MicroRNA-27b Contributes to Lipopolysaccharide-mediated Peroxisome Proliferator-activated Receptor γ (PPARγ) mRNA Destabilization
Open accessAbstract
Peroxisome proliferator-activated receptor gamma (PPARgamma) gained considerable interest as a therapeutic target during chronic inflammatory diseases. Remarkably, the pathogenesis of diseases such as multiple sclerosis or Alzheimer is associated with impaired PPARgamma expression. Considering that regulation of PPARgamma expression during inflammation is largely unknown, we were interested in elucidating underlying mechanisms. To this end, we initiated an inflammatory response by exposing primary human macrophages to lipopolysaccharide (LPS) and observed a rapid decline of PPARgamma1 expression. Because promoter activities were not affected by LPS, we focused on mRNA stability and noticed a decreased mRNA half-life. As RNA stability is often regulated via 3'-untranslated regions (UTRs), we analyzed the impact of the PPARgamma-3'-UTR by reporter assays using specific constructs. LPS significantly reduced luciferase activity of the pGL3-PPARgamma-3'-UTR, suggesting that PPARgamma1 mRNA is destabilized. Deletion or mutation of a potential microRNA-27a/b (miR-27a/b) binding site within the 3'-UTR restored luciferase activity. Moreover, inhibition of miR-27b, which was induced upon LPS exposure, partially reversed PPARgamma1 mRNA decay, whereas miR-27b overexpression decreased PPARgamma1 mRNA content. In addition, LPS further reduced this decay. The functional relevance of miR-27b-dependent PPARgamma1 decrease was proven by inhibition or overexpression of miR-27b, which affected LPS-induced expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-6. We provide evidence that LPS-induced miR-27b contributes to destabilization of PPARgamma1 mRNA. Understanding molecular mechanisms decreasing PPARgamma might help to better appreciate inflammatory diseases.
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Written from the paper’s full text.
TL;DR
LPS destabilizes PPARγ1 mRNA in human macrophages, and miR-27b, induced by LPS in an NFκB-dependent manner, contributes to this decay via a miR-27a/b binding site in the PPARγ 3′-UTR. Modulating miR-27b affects LPS-induced TNFα and IL-6 expression, linking this mechanism to inflammatory cytokine regulation.
Key findings
- LPS (1 µg/ml) reduced PPARγ1 mRNA in differentiated THP-1 macrophages to ~20% after 3 h and decreased PPARγ protein with a minimum at 8 h; PPARγ1 mRNA half-life fell from 173 to 99 min with DRB plus LPS.
- The PPARγ 3′-UTR reporter was reduced by LPS to ~65% after 3 h and ~50% after 6 h relative to pGL3-control; deletion or mutation of the miR-27 binding site abolished this LPS-mediated reduction.
- LPS induced miR-27b 2.3-fold and miR-27a 1.6-fold; anti-miR-27b prevented LPS-dependent PPARγ1 mRNA reduction in a concentration-dependent manner, whereas miR-27b mimic reduced PPARγ1 mRNA and LPS further reduced it.
- Functionally, miR-27b overexpression relieved rosiglitazone-mediated inhibition of LPS-induced TNFα and IL-6, while anti-miR-27b lowered TNFα and IL-6 induction upon LPS exposure.
Methods
- Primary human macrophages were isolated from buffy coats and differentiated for 7 days; THP-1 monocytes were differentiated into macrophages with 50 nM PMA. Cells were stimulated with LPS (1 µg/ml), TNFα (15 ng/ml), IFNγ (10 units/ml), or IFNγ plus LPS.
- PPARγ1 mRNA, miRNA, and cytokine expression were measured by qPCR; PPARγ protein by Western analysis; PPARγ promoter, PPRE, and PPARγ-3′-UTR activity by luciferase reporter assays using wild-type, ΔmiR-27, and C83A/U84G constructs.
- mRNA stability was assessed with DRB; miRNA function was tested by transfecting miR-27b mimic or anti-miR-27a/b inhibitors. Experiments were performed at least three times, with paired or unpaired Student’s t tests and significance at p < 0.05, 0.01, or 0.001.
Limitations
- The paper states that actinomycin D and DRB can differently affect mRNA half-life estimates, and that actinomycin D may affect mRNA stability by inducing translocalization of ARE-binding proteins.
- The paper states that additional regulatory mechanisms likely operate: LPS further decreased PPARγ1 mRNA despite miR-27b overexpression, miR-27b overexpression did not significantly reduce PPARγ mRNA half-life in the absence of LPS, and TNFα experiments suggested other mechanisms besides miR-27b-dependent down-regulation.
- Evident from the text: the work relies on in vitro human macrophage/THP-1 systems and reporter constructs, without in vivo validation of the miR-27b–PPARγ1 axis in inflammatory disease models.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
8 of 14 cited sources checked · 2 supported · 1 flagged · accuracy not yet measured
- Findingcitation
NFκB inhibition with Bay11-7082 abrogates LPS-mediated PPARγ1 mRNA decay.
“Inhibition of NFB with Bay11-7082 abrogated LPS-mediated PPAR␥1 mRNA decay, which is corroborated by the work of Necela et al. (22).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Necela et al. [22] Necela, 2008, Immunology source
The Results section reports that NF-κB inhibitors, including Bay 11-7085, blocked LPS-mediated downregulation of PPARγ. But its mRNA-stability experiment found that LPS had no significant effect on PPARγ mRNA degradation; the paper attributes the reduction to inhibited mRNA synthesis, not decay. It therefore does not corroborate the claimed mechanism or the specific Bay11-7082 result. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
- Findingcitation
LPS time-dependently reduces PPARγ1 mRNA and protein amounts in macrophages.
“LPS, a classical pro-inflammatory stimulus time-dependently reduced PPAR␥1 mRNA and protein amounts in macrophages, which is in line with the work of Necela et al. (22) showing a reduction of PPAR␥ mRNA in murine RAW264.7 macrophages.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Necela et al. [22] Necela, 2008, Immunology source
- Premisecitation
Chronic inflammatory disease conditions often reveal impaired PPARγ abundance.
“Interestingly, these disease conditions often revealed impaired PPAR␥ abundance (16,17).”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [16] Kobayashi, 2005, Ann. Allergy Asthma Immunol. source
- cites [17] Dubuquoy, 2006, Gut source
The Introduction reports 60% lower colonic PPARγ expression in patients with ulcerative colitis and impaired expression in a mouse model of ileitis. It also says expression in Crohn’s disease patients was comparable to controls, so it does not establish that chronic inflammatory disease conditions generally or often show reduced PPARγ abundance. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
Studies in PPARγ knock-out macrophages showed these cells express higher amounts of pro-inflammatory mediators such as IL-6.
“Studies in PPAR␥ knock-out macrophages supported the importance of PPAR␥, because these cells expressed higher amounts of pro-inflammatory mediators such as IL-6 (22).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [22] Necela, 2008, Immunology source
- Findingown data
LPS induces a 2.3-fold increase of miR-27b.
“In line, we observed a 2.3-fold increase of miR-27b in response to LPS, which is comparable to the induction of miR-146a after 2 h of LPS exposure in THP-1 cells (6).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [6] Taganov, 2006, Proc. Natl. Acad. Sci. U.S.A. source
The Results report rapid LPS-induced miR-146 expression in THP-1 cells, supporting the cited comparison in general. Our copy does not give a 2-hour fold change for miR-146a, so it does not establish that the induction was comparable in magnitude to 2.3-fold. The miR-27b result is explicitly the citing authors’ own observation, not a result attributed to this source. (LLM, conf=0.85)
Experimental — accuracy not yet measured
- Findingown data
Deletion or mutation of the miR-27 site within the PPARγ-3'UTR completely abolishes the LPS-mediated reduction of luciferase activity.
“Deletion as well as mutation of the miR-27 site completely abolished the LPS-mediated reduction of luciferase activity (Fig. 3C), suggesting a miR-27-dependent mechanism.”
Quote in the paperSubstantial claim - Findingown data
LPS alone does not alter basal luciferase expression in the PPRE reporter assay.
“LPS alone did not alter basal luciferase expression (data not shown).”
Quote in the paperNot a substantial claim - Findingown data
LPS exposure attenuates PPARγ promoter 1 luciferase activity to about 60% after 6 h.
“LPS exposure attenuated PPAR␥ promoter 1 luciferase activity to ϳ60% after 6 h”
Quote in the paperSubstantial claim - Findingown data
LPS significantly reduces luciferase activity of the PPARγ-3'UTR-containing vector to about 65% after 3 h and 50% after 6 h relative to pGL3-control.
“LPS significantly reduced luciferase activity of the PPAR␥-3Ј-UTR containing vector to ϳ65% after 3 h and to 50% after 6 h relative to pGL3-control (Fig. 2C)”
Quote in the paperSubstantial claim - Findingown data
In differentiated THP-1 macrophages, 3 h of LPS exposure significantly decreases PPARγ1 mRNA to about 20% of unstimulated cells.
“3 h of LPS exposure significantly decreased PPAR␥1 mRNA to ϳ20% in comparison to unstimulated cells.”
Quote in the paperSubstantial claim - Findingown data
LPS prestimulation prevents rosiglitazone-induced PPARγ transactivation in differentiated THP-1 macrophages.
“Rosiglitazone, a well established synthetic PPAR␥ agonist (20), induced luciferase expression in control cells, whereas prestimulation with LPS prevented transactivation by rosiglitazone (Fig. 1E).”
Quote in the paperSubstantial claim - Findingown data
LPS causes a time-dependent reduction of PPARγ protein with a minimum at 8 h and subsequent increase.
“Western analysis showed a time-dependent reduction of protein expression with a minimum at 8 h, again increasing afterward (Fig. 1D).”
Quote in the paperSubstantial claim - Findingown data
LPS reduces the PPARγ1 mRNA half-life from 173 to 99 min.
“Calculating the halflife of PPAR␥1 revealed a reduction from 173 to 99 min, indicating that the mRNA decrease is caused by destabilization.”
Quote in the paperSubstantial claim - Findingown data
LPS exposure causes a rapid decline of PPARγ1 expression in primary human macrophages.
“we initiated an inflammatory response by exposing primary human macrophages to lipopolysaccharide (LPS) and observed a rapid decline of PPAR␥1 expression.”
- Also stated in: § RESULTS · plain
“Upon LPS exposure, both variants were down-regulated (Fig. 1A).”
Quote in the paperSubstantial claim - Also stated in: § RESULTS · plain
- Findingown data
A 2-fold induction of miR-27b by mimic decreases PPARγ1 mRNA to approximately 70%.
“miR-27b by transfecting cells with miR-27b mimic decreased PPAR␥1 mRNA to ϳ70% (supplemental Fig. S2).”
Quote in the paperSubstantial claim - Findingown data
miR-27b overexpression relieves rosiglitazone-mediated inhibition of LPS-induced TNFα and IL-6 expression.
“Whereas pretreating macrophages with rosiglitazone for 1 h reduced LPS-induced expression of TNF␣ and IL-6, overexpression of miR-27b relieved rosiglitazone-mediated inhibition (Fig. 7, A and C).”
Quote in the paperSubstantial claim - Findingown data
Anti-miR-27b prevents LPS-dependent PPARγ1 mRNA reduction in a concentration-dependent manner compared with a negative control.
“Anti-miR-27b prevented LPS-dependent PPAR␥1 mRNA reduction in a concentration-dependent manner compared with a negative control (Fig. 5A).”
Quote in the paperSubstantial claim - Findingown data
Inhibition of NFκB prevents the LPS-induced PPARγ1 mRNA decrease.
“and the PPAR␥1 mRNA decrease (Fig. 4B).”
Quote in the paperSubstantial claim - Findingown data
Inhibition of NFκB prevents LPS-induced miR-27b up-regulation.
“Inhibition of NFB prevented LPS-induced miR-27b up-regulation (Fig. 4A)”
Quote in the paperSubstantial claim - Findingnone given
Prolonged LPS exposure allows recovery of PPARγ mRNA to almost basal levels after 24 h.
“Prolonged LPS exposure allowed to recover PPAR␥ mRNA to almost basal levels after 24 h.”
Quote in the paperNot a substantial claim - Findingown data
LPS-induced miR-27b induction is at least partially NFκB-dependent.
“We also observed that induction of miR-27b is at least partially NFBdependent.”
Quote in the paperSubstantial claim - Findingown data
Inhibition of miR-27b partially reverses PPARγ1 mRNA decay.
“inhibition of miR-27b, which was induced upon LPS exposure, partially reversed PPAR␥1 mRNA decay”
Quote in the paperSubstantial claim - Findingown data
LPS induces miR-27b 2.3-fold in macrophages.
“We observed a 2.3-fold induction of miR-27b (Fig. 4A)”
Quote in the paperSubstantial claim - Findingown data
Deletion or mutation of the miR-27 site within the PPARγ-3'UTR reporter construct substantiates miR-27b-dependent mRNA decay.
“Deletion or mutation of the miR-27 site within the PPAR␥-3Ј-UTR reporter construct substantiated a miR-27b-dependent mRNA decay.”
Quote in the paperSubstantial claim - Findingown data
Inhibiting miR-27b impairs LPS-induced reduction of PPARγ1 mRNA half-life.
“Inhibition of miR-27b impaired the ability of LPS to reduce the mRNA halflife (Fig. 5B), verifying the impact of miR-27b on PPAR␥1 destabilization.”
Quote in the paperSubstantial claim - Findingown data
In macrophages transfected with miR-27b mimic, LPS treatment further reduces PPARγ1 mRNA expression.
“However, LPS treatment further reduced PPAR␥1 mRNA expression (Fig. 6B).”
Quote in the paperSubstantial claim - Findingown data
Experiments with DRB imply PPARγ1 mRNA destabilization upon LPS exposure.
“Experiments with the transcription inhibitor DRB implied PPAR␥1 mRNA destabilization upon LPS exposure.”
Quote in the paperSubstantial claim - Findingown data
Inhibiting miR-27b lowers TNFα and IL-6 induction upon LPS exposure.
“Inhibiting miR-27b by transfecting cells with anti-miR-27b lowered TNF␣ and IL-6 induction upon LPS exposure in comparison to the controls (Fig. 7, B and D).”
Quote in the paperSubstantial claim - Findingown data
Rosiglitazone pretreatment reduces LPS-induced TNFα and IL-6 expression.
“Whereas pretreating macrophages with rosiglitazone for 1 h reduced LPS-induced expression of TNF␣ and IL-6, overexpression of miR-27b relieved rosiglitazone-mediated inhibition (Fig. 7, A and C).”
Quote in the paperSubstantial claim - Findingreasoning
Modulating miR-27b affects TNFα and IL-6 mRNA amounts.
“Thus, overexpressing or inhibiting miR-27b affected TNF␣ and IL-6 mRNA amount.”
Quote in the paperSubstantial claim - Findingown data
Transfection with miR-27b mimic reduces PPARγ1 mRNA in a concentration-dependent manner.
“In line, transfection with the miR-27b mimic reduced PPAR␥1 mRNA in a concentration-dependent manner (Fig. 6A).”
Quote in the paperSubstantial claim - Findingown data
LPS significantly reduces luciferase activity of pGL3-PPARγ-3'UTR construct.
“Luciferase assays with a pGL3-PPAR␥-3Ј-UTR construct demonstrated the importance of the PPAR␥-3Ј-UTR, because LPS significantly reduced luciferase activity.”
Quote in the paperSubstantial claim - Findingown data
In absence of LPS, miR-27b overexpression does not significantly reduce PPARγ mRNA half-life compared to control.
“Interestingly miR-27b overexpression did not significantly reduce PPAR␥ mRNA half-life in comparison to siControltransfected cells in the absence of LPS (Fig. 6C).”
Quote in the paperSubstantial claim - Findingown data
miR-27b overexpression decreases PPARγ1 mRNA content.
“whereas miR-27b overexpression decreased PPAR␥1 mRNA content.”
Quote in the paperSubstantial claim - Findingown data
TNFα induces miR-27b expression.
“TNF␣ also induced miR-27b expres-sion (supplemental Fig. S2B).”
Quote in the paperSubstantial claim - Findingown data
There is an inverse correlation between PPARγ1 mRNA and miR-27b expression over the time of LPS treatment.
“analyzing expression of miR-27b and PPAR␥1 in response to the time of LPS treatment revealed an inverse correlation between PPAR␥1 mRNA and miR-27b expression (Fig. 4C).”
Quote in the paperSubstantial claim - Findingown data
Inhibiting miR-27a does not affect LPS-induced PPARγ1 mRNA reduction.
“Inhibition of miR-27a showed no effect on PPAR␥1 reduction upon LPS exposure (supple- mental Fig. S1B).”
Quote in the paperNot a substantial claim - Findingown data
IFNγ plus LPS reduces PPARγ1 mRNA.
“Interestingly, stimulation with IFN␥ plus LPS also reduced PPAR␥1 mRNA, suggesting that TLR4 activation overrules IFN␥ signaling (supplemental Fig. S2A).”
Quote in the paperNot a substantial claim - Findingown data
IFNγ increases PPARγ1 mRNA.
“TNF␣ also decreased PPAR␥1 mRNA expression albeit to a lesser extent than LPS, whereas IFN␥ increased PPAR␥1 mRNA.”
Quote in the paperNot a substantial claim - Findingown data
TNFα decreases PPARγ1 mRNA expression to a lesser extent than LPS.
“TNF␣ also decreased PPAR␥1 mRNA expression albeit to a lesser extent than LPS, whereas IFN␥ increased PPAR␥1 mRNA.”
Quote in the paperNot a substantial claim - Findingown data
LPS induces miR-27a 1.6-fold in macrophages.
“and a 1.6-fold induction of miR-27a (supplemental Fig. S1A).”
Quote in the paperNot a substantial claim - Findingown data
Inhibition or overexpression of miR-27b affects LPS-induced expression of the pro-inflammatory cytokines TNFα and IL-6.
“PPAR␥1 decrease was proven by inhibition or overexpression of miR-27b, which affected LPS-induced expression of the pro-inflammatory cytokines tumor necrosis factor ␣ (TNF␣) and interleukin (IL)-6.”
Quote in the paperSubstantial claim - Interpretationown data
The LPS-induced decrease in PPARγ1 mRNA is caused by destabilization.
“indicating that the mRNA decrease is caused by destabilization.”
- Also stated in: § Abstract · hedged
“suggesting that PPAR␥1 mRNA is destabilized.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Reduction of PPARγ promoter 1 activity to 60% is negligible for the LPS-induced PPARγ1 mRNA decrease.
- Also stated in: § Abstract · hedged
- Interpretationown data
The PPARγ 3'UTR is important for PPARγ1 mRNA stability.
“underlining the importance of the 3Ј-UTR for PPAR␥1 mRNA stability.”
Quote in the paperSubstantial claim - Interpretationown data
The LPS-mediated reduction of luciferase activity is miR-27-dependent.
“suggesting a miR-27-dependent mechanism.”
Quote in the paperSubstantial claim - Interpretationreasoning
Stimulation with TNFα reduces PPARγ1 levels likely by miR-27b induction.
“In line, stimulation with TNF␣ reduced PPAR␥1 levels likely by miR-27b induction, while IFN␥ (not activating NFB) rather induced PPAR␥1 expression.”
Quote in the paperSubstantial claim - Interpretationreasoning
Additional regulatory mechanisms beyond miR-27b contribute to LPS-induced PPARγ1 mRNA decrease.
“Taking into consideration that LPS further decreased PPAR␥1 mRNA despite its reduction by miR-27b overexpression suggests additional regulatory mechanisms likely by an ARE-binding protein.”
- Also stated in: § Data availability · hedged
“as a 2-fold induction of miR-27b reduced PPAR␥1 mRNA to a lower extent than LPS but overexpression of miR-27b did not alter mRNA stability, points to additional regulatory mechanisms.”
Quote in the paperSubstantial claim - Also stated in: § Data availability · hedged
- Interpretationown data
miR-27b is a prerequisite for LPS-induced PPARγ mRNA destabilization.
“Nevertheless, abrogating a luciferase decrease upon LPS by deletion of the miR-27 binding side or mutation of the seed region revealed that miR-27b is a prerequisite for LPS-induced PPAR␥ mRNA destabilization.”
Quote in the paperSubstantial claim - Interpretationown data
TLR4 activation overrules IFNγ signaling.
“Interestingly, stimulation with IFN␥ plus LPS also reduced PPAR␥1 mRNA, suggesting that TLR4 activation overrules IFN␥ signaling (supplemental Fig. S2A).”
Quote in the paperNot a substantial claim - Interpretationown data
Reduced promoter 1 activity is negligible because this transcript variant is only minimally expressed in fully differentiated macrophages.
“appears to be negligible because this transcript variant was only minimally expressed in fully differentiated macrophages.”
Quote in the paperSubstantial claim - Interpretationown data
miR-27b acts via mRNA destabilization rather than translational control.
“Inhibition of miR-27b prevented PPAR␥1 mRNA decay and thus, points to mRNA destabilization rather than translational control by miR-27b.”
Quote in the paperSubstantial claim - Interpretationown data
The PPARγ-3'UTR is important for LPS-induced reduction.
“Luciferase assays with a pGL3-PPAR␥-3Ј-UTR construct demonstrated the importance of the PPAR␥-3Ј-UTR, because LPS significantly reduced luciferase activity.”
Quote in the paperSubstantial claim - Interpretationown data
Transcriptional regulation does not account for LPS-induced PPARγ1 mRNA reduction.
“Investigating PPAR␥ promoter activity, we ruled out transcriptional regulation.”
Quote in the paperSubstantial claim - Interpretationreasoning
The NFκB-dependent PPARγ1 mRNA decrease results at least in part from NFκB-dependent induction of miR-27b upon LPS exposure.
“We conclude that the NFB-dependent PPAR␥1 mRNA decrease results at least in part from the NFB-dependent induction of miR-27b upon LPS exposure.”
Quote in the paperSubstantial claim - Interpretationreasoning
A minor reduction of promoter 3 activity after 6 h of LPS exposure unlikely accounts for a 90% decrease of mRNA.
“Moreover, a minor reduction of promoter 3 activity after 6 h of LPS exposure unlikely accounts for a 90% decrease of mRNA.”
Quote in the paperSubstantial claim - Interpretationown data
Besides miR-27b-dependent down-regulation, other regulatory mechanisms operate.
“Moreover, inhibiting miR-27b by transfecting cells with anti-miR- 27b not only prevented the reduc- tion but even allowed induction of PPAR␥1 mRNA (supplemental Fig. S2C), suggesting that besides miR-27b-dependent down-regulation, other regulatory mechanisms are operating.”
Quote in the paperSubstantial claim - Premisecitation
PPARγ has anti-inflammatory effects by attenuating production of pro-inflammatory mediators.
“PPAR␥ is well established for its anti-inflammatory effects in attenuating the production of pro-inflammatory mediators (12).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Ricote, 1998, Nature source
- Interpretationown data
miR-27b impacts PPARγ1 destabilization.
“verifying the impact of miR-27b on PPAR␥1 destabilization.”
Quote in the paperSubstantial claim - Interpretationown data
LPS-induced miR-27b contributes to destabilization of PPARγ1 mRNA.
“We provide evidence that LPSinduced miR-27b contributes to destabilization of PPAR␥1 mRNA.”
- Also stated in: § Abstract · plain
“Here we provide evidence that PPAR␥1 mRNA is destabilized by miR-27b, which is induced in macrophages upon lipopolysaccharide (LPS) exposure.”
Quote in the paperSubstantial claim- The authors state this as an assumption: Reduction of PPARγ promoter 1 activity to 60% is negligible for the LPS-induced PPARγ1 mRNA decrease.
- Also stated in: § Abstract · plain
- Classified as probably not a substantial claim. 6
- May combine two claims. 9
- The quote only partly states this claim. 1
Classified as probably not a substantial claim. May combine two claims.
PremisecitationIn macrophages, PPARγ represses inducible nitric-oxide synthase induction and concomitant NO production.
“In macrophages PPAR␥ represses inducible nitric-oxide (NO) synthase induction as well as concomitant NO production (11)”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [11] Li, 2000, Mol. Cell. Biol. source
The Abstract states that liganded PPARγ inhibits induction of the iNOS gene in monocytes/macrophages, and the Results report repression of LPS-induced iNOS promoter activity. The cited paper does not report a corresponding reduction in NO production, so that part of the claim is unsupported. (LLM, conf=0.86)
Experimental — accuracy not yet measured
May combine two claims.
FindingcitationPPARγ-3'UTR contains several ARE1 and ARE4 sites and a potential miR-27a/b binding site.
“In silico analysis showed several ARE 1 (AUUUA) and ARE 4 (12-mer A/U, max.one mismatch) sites (33) as well as a potential miR-27a/b binding site.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [33] Sharova, 2009, DNA Res. source
The Results and discussion section (Multivariate analysis of gene structural features; page unavailable) defines ARE1 as AUUUA and ARE4 as A/U 12-mers with no more than one mismatch. It does not report that several such sites occur in the PPARγ 3′-UTR. The miR-27a/b clause follows citation (33) and is not assessed as attributed to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationmiR-146 and miR-155 negatively regulate Toll-like receptor signaling.
“miR-146 and miR-155 gained special interest and are well described for negatively regulating Toll-like receptor (TLR)-signaling (6).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [6] Taganov, 2006, Proc. Natl. Acad. Sci. U.S.A. source
The Discussion (page unavailable) proposes that miR-146 negatively regulates TLR signaling through a feedback loop involving IRAK1 and TRAF6, but describes that role as a suggestion rather than an established effect. It reports that miR-155 is induced by LPS; it does not show that miR-155 negatively regulates TLR signaling. (LLM, conf=0.90)
Experimental — accuracy not yet measured
May combine two claims.
Findingown dataLPS decreases total PPARγ1 mRNA in primary macrophages with a nadir around 6 h and recovery nearly to control levels by 24 h.
“There was a slight increase of PPAR␥1 mRNA after 30 min followed by a rapid decrease of PPAR␥1 with the lowest mRNA amounts after 6 h.Extended incubation periods allowed to recover PPAR␥1 mRNA content nearly reaching control levels after 24 h of LPS treatment (Fig. 1B).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataDRB alone reduces PPARγ1 mRNA to about 60% after 3 h, and DRB plus LPS decreases it to 26% relative to untreated cells.
“DRB alone reduced PPAR␥1 mRNA expression to ϳ60% after 3 h, whereas DRB plus LPS decreased mRNA to 26% relative to untreated cells (Fig. 2B).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe PPARγ-3'UTR contains distinct AREs and a potential binding site for miR-27a/b.
“The in-depth analysis of the PPAR␥-3Ј-UTR (TargetScanHuman 5.1) revealed distinct AREs and a potential binding site for miR-27a/b (Fig. 3A).”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataUsing actinomycin D, we observed similar results (LPS-induced destabilization).
“Using actinomycin D we observed similar results.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataInhibiting miR-27b with anti-miR-27b prevents TNFα-induced reduction and allows induction of PPARγ1 mRNA.
“Moreover, inhibiting miR-27b by transfecting cells with anti-miR- 27b not only prevented the reduc- tion but even allowed induction of PPAR␥1 mRNA (supplemental Fig. S2C), suggesting that besides miR-27b-dependent down-regulation, other regulatory mechanisms are operating.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationPPARγ is important to shape an anti-inflammatory macrophage phenotype and appears crucial for dampening inflammation.
“Thus, PPAR␥ is important to shape an anti-inflammatory macrophage phenotype and appears crucial for dampening inflammation (15).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Serhan, 2005, Nat. Immunol. source
May combine two claims.
InterpretationreasoningDecreased PPARγ expression prolongs inflammation and attenuates resolution of inflammation.
“We suggest that decreased PPAR␥ expression prolongs inflammation and thus, attenuates resolution of inflammation.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTLR activation triggers induction of miRNAs such as miR-21 or miR-132.
“However, TLR activation also triggers induction of miRNAs such as miR-21 or miR-132 (5)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] Sheedy, 2008, Ann. Rheum. Dis. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationInhibiting NFκB decreases expression of inflammatory cytokines such as IL-1, TNFα, or IL-6.
“Moreover, inhibiting nuclear factor B (NFB) decreases expression of inflammatory cytokines such as interleukin (IL)-1, tumor necrosis factor ␣ (TNF␣) or IL-6 (12).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Ricote, 1998, Nature source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationmiRNAs play an eminent role in controlling immune responses and have been associated with several inflammatory diseases.
“Functionally miRNAs play an eminent role in controlling immune responses and have been associated with several inflammatory diseases (5).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [5] Sheedy, 2008, Ann. Rheum. Dis. source
The paper relies on this without support.
Mechanisms attenuating PPARγ expression remained obscure.
“Because mechanisms attenuating PPAR␥ expression remained obscure, we investigated regulation of PPAR␥ during inflammation.”
The authors state this as an assumption.
Reduction of PPARγ promoter 1 activity to 60% is negligible for the LPS-induced PPARγ1 mRNA decrease.
“we assumed that reduction of the promoter 1 activity to 60% is negligible for the LPS-induced PPAR␥1 mRNA decrease.”
The authors state this as an assumption.
Inflammatory signals in general provoke PPARγ mRNA decay.
“we suggest that inflammatory signals in general provoke a mRNA decay.This assumption is supported by the notion that NFB, a major inflammatory transcription factor, is involved.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Reported anti-miR dose falls outside the stated protocol range
MinorThe transfection procedure specifies 100-300 pmol of anti-miR inhibitor, while Figure 5A reports a 50-pmol condition.
“1.5 ϫ 10 6 cells were transfected with 100 -300 pmol of anti-miR-27a/b inhibitor”
“A, primary human macrophages were transfected with different concentrations (50, 100, 150 pmol) of anti-miR-27b or a negative control.”
Conflicting LPS pretreatment times for the PPRE assay
MinorThe results describe 4 hours of LPS pretreatment before rosiglitazone, whereas the Figure 1E caption specifies 6 hours.
“pretreated cells the next day with 1 g/ml LPS for 4 h followed by stimulation with 5 M rosiglitazone for 4 h”
“E, PPRE reporter activity was measured in differentiated THP-1 macrophages after pretreatment with 1 g/ml LPS for 6 h, followed by 5 M rosiglitazone for 4 h.”
Figure 6C treatment timing conflicts with the transfection protocol
MinorThe transfection procedure says cells were cultured for another 48 hours before experiments, but the Figure 6C caption says DRB treatment began 2 hours after transfection.
“Following transfection cells were seeded on 3-cm Primaria dishes and cultured for another 48 h prior to experiments.”
“C, primary human macrophages were transfected with 10 pmol of miR-27b mimic or siControl and treated for 1-3 h with 100 M DRB 2 h after transfection.”
Abstract says LPS did not affect promoter activity
MinorThe abstract says promoter activities were not affected by LPS, but the results report that LPS reduced promoter 1 activity to about 60% after 6 hours.
“Because promoter activities were not affected by LPS, we focused on mRNA stability”
“LPS exposure attenuated PPAR␥ promoter 1 luciferase activity to ϳ60% after 6 h”
Cites
Taganov, K. D., Boldin, M. P., Chang, K.-J., & Baltimore, D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605298103 · Cited by 4,317 · see citing works
The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J., & Glass, C. K. (1998) · Nature · doi:10.1038/34178 · Cited by 3,525 · see citing works
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932 · see citing works
Many roads to maturity: microRNA biogenesis pathways and their regulation
Winter, J. J., Jung, S., Keller, S., Gregory, R. I., & Diederichs, S. (2009) · Nature Cell Biology · doi:10.1038/ncb0309-228 · Cited by 2,646 · see citing works
Resolution of inflammation: the beginning programs the end
Serhan, C. N., & Savill, J. (2005) · Nature Immunology · doi:10.1038/ni1276 · Cited by 2,552 · see citing works
Yki-Järvinen, H. (2004) · New England Journal of Medicine · doi:10.1056/nejmra041001 · Cited by 1,830 · see citing works
Tili, E., Michaille, J.-J., Cimino, A., Costinean, S., Dumitru, C. D., Adair, B., Fabbri, M., Alder, H., Liu, C. G., Calin, G. A., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5082 · Cited by 1,304 · see citing works
The Organization, Promoter Analysis, and Expression of the Human PPARγ Gene
Lluis Fajas, A., Auboeuf, D., Raspé, E., Schoonjans, K., Lefebvre, A., Saladin, R., Najib, J., Laville, M., Fruchart, J., Deeb, S. S., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.30.18779 · Cited by 1,188 · see citing works
Getting to the Root of miRNA-Mediated Gene Silencing
Eulálio, A., Huntzinger, E., & Izaurralde, E. (2008) · Cell · doi:10.1016/j.cell.2007.12.024 · Cited by 1,071 · see citing works
Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis
Stańczyk, J., Pedrioli, D. M. L., Brentano, F., Sánchez‐Pernaute, O., Kolling, C., Gay, R. E., Detmar, M. J., Gay, S., & Kyburz, D. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23386 · Cited by 905 · see citing works
Tugwood, J. D., Issemann, I., Anderson, R. G., Bundell, K. R., McPheat, W. L., & Green, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05072.x · Cited by 895 · see citing works
microRNA-155 Regulates the Generation of Immunoglobulin Class-Switched Plasma Cells
Vigorito, E., Perks, K. L., Abreu‐Goodger, C., Bunting, S., Xiang, Z., Kohlhaas, S. L., Das, P. P., Miska, E. A., Rodriguez, A., Bradley, A., et al. (2007) · Immunity · doi:10.1016/j.immuni.2007.10.009 · Cited by 763 · see citing works
RNA stabilization by the AU‐rich element binding protein, HuR, an ELAV protein
Peng, S., Chen, C. A., Xu, N., & Shyu, A. (1998) · The EMBO Journal · doi:10.1093/emboj/17.12.3461 · Cited by 739 · see citing works
Ricote, M., Huang, J. T., Lluis Fajas, A., Li, A. I., Welch, J. S., Najïb, J., Witztum, J. L., Auwerx, J. H., Palinski, W., & Glass, C. K. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7614 · Cited by 721 · see citing works
Expression of microRNA‐146 in rheumatoid arthritis synovial tissue
Nakasa, T., Miyaki, S., Okubo, A., Hashimoto, M., Nishida, K., Ochi, M., & Asahara, H. (2008) · Arthritis & Rheumatism · doi:10.1002/art.23429 · Cited by 678 · see citing works
Sharova, L. V., Sharov, A. A., Nedorezov, T., Piao, Y., Shaik, N., & Ko, M. S. H. (2009) · DNA Research · doi:10.1093/dnares/dsn030 · Cited by 591 · see citing works
PPARγ as a new therapeutic target in inflammatory bowel diseases
Dubuquoy, L., Rousseaux, C., Thuru, X., Peyrin-Biroulet, L., Romano, O., Chavatte, P., Chamaillard, M., & Desreumaux, P. (2006) · Gut · doi:10.1136/gut.2006.093484 · Cited by 450 · see citing works
A role of miR‐27 in the regulation of adipogenesis
Lin, Q., Gao, Z., Alarcon, R. M., Ye, J., & Yun, Z. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.06967.x · Cited by 438 · see citing works
Impaired expression of peroxisome proliferator-activated receptor γ in ulcerative colitis
Dubuquoy, L., Jansson, E. Å., Deeb, S. S., Rakotobé, S., Karoui, M., Colombel, J., Auwerx, J. H., Pettersson, S., & Desreumaux, P. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00271-3 · Cited by 425 · see citing works
microRNA miR-27b impairs human adipocyte differentiation and targets PPARγ
Karbiener, M., Fischer, C., Nowitsch, S., Opriessnig, P., Papak, C., Ailhaud, G., Dani, C., Amri, E.-Z., & Scheideler, M. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.09.098 · Cited by 409 · see citing works
Elbrecht, A., Chen, Y., Cullinan, C. A., Hayes, N. S., Leibowitz, M. D., Moller, D. E., & Berger, J. P. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1044 · Cited by 384 · see citing works
Li, M., Pascual, G., & Glass, C. K. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.13.4699-4707.2000 · Cited by 377 · see citing works
Sastre, M., Dewachter, I., Rossner, S., Bogdanovic, N., Rosen, E., Borghgraef, P., Evert, B. O., Dumitrescu-Ozimek, L., Thal, D. R., Landreth, G., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503839103 · Cited by 373 · see citing works
PPARγ3 mRNA: a distinct PPARγ mRNA subtype transcribed from an independent promoter
Fajas, L., Fruchart, J., & Auwerx, J. H. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01273-3 · Cited by 337 · see citing works
Loflin, P. T., Chen, C.-Y. A., & Shyu, A. B. (1999) · Genes & Development · doi:10.1101/gad.13.14.1884 · Cited by 293 · see citing works
Moschos, S. A., Williams, A. E., Perry, M. M., Birrell, M. A., Belvisi, M. G., & Lindsay, M. A. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-240 · Cited by 284 · see citing works
Adding fuel to fire: microRNAs as a new class of mediators of inflammation
Sheedy, F. J., & O'Neill, L. A. J. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2008.100289 · Cited by 246 · see citing works
Rosiglitazone for Active Ulcerative Colitis: A Randomized Placebo-Controlled Trial
Lewis, J. D., Lichtenstein, G. R., Deren, J. J., Sands, B. E., Hanauer, S. B., Katz, J. A., Lashner, B. A., Present, D. H., Chuai, S., Ellenberg, J. H., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.12.012 · Cited by 229 · see citing works
The RNA-binding Protein HuR Regulates the Expression of Cyclooxygenase-2
Sengupta, S., Jang, B., Wu, M.-T., Paik, J., Furneaux, H., & Hla, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301813200 · Cited by 163 · see citing works
Necela, B. M., Su, W., & Thompson, E. A. (2008) · Immunology · doi:10.1111/j.1365-2567.2008.02849.x · Cited by 140 · see citing works
Peroxisome Proliferator-Activated Receptors (PPARs) and the Human Skin
Sertznig, P., Seifert, M., Tilgen, W., & Reichrath, J. (2008) · American Journal of Clinical Dermatology · doi:10.2165/00128071-200809010-00002 · Cited by 135 · see citing works
microRNA miR-27b impairs human adipocyte differentiation and targets PPARg
Karbiener, M., Fischer, C., Nowitsch, S., et al. (2010) · Cited by 117 · see citing works
Harrold, S. M., Genovese, C., Kobrin, B. J., Morrison, S. L., & Milcarek, C. (1991) · Analytical Biochemistry · doi:10.1016/0003-2697(91)90500-s · Cited by 111 · see citing works
Therapeutic Use of Agonists of the Nuclear Receptor PPARγ in Alzheimers Disease
Landreth, G. E. (2007) · Current Alzheimer Research · doi:10.2174/156720507780362092 · Cited by 108 · see citing works
Taylor, G. A., Thompson, M. J., Lai, W. S., & Blackshear, P. J. (1996) · Molecular Endocrinology · doi:10.1210/mend.10.2.8825554 · Cited by 108 · see citing works
Klotz, L., Schmidt, M., Giese, T., Sastre, M., Knolle, P. A., Klockgether, T., & Heneka, M. T. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.8.4948 · Cited by 102 · see citing works
Posttranscriptional Mechanisms Regulating the Inflammatory Response
Stoecklin, G., & Anderson, P. (2006) · Advances in immunology · doi:10.1016/s0065-2776(05)89001-7 · Cited by 94 · see citing works
Johann, A. M., von Knethen, A., Lindemann, D., & Brüne, B. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401832 · Cited by 83 · see citing works
Self-citationPPARγ1 attenuates cytosol to membrane translocation of PKCα to desensitize monocytes/macrophages
von Knethen, A., Soller, M., Tzieply, N., Weigert, A., Johann, A. M., Jennewein, C., Köhl, R., & Brüne, B. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200605038 · Cited by 78 · see citing works
Self-citationDelayed activation of PPARγ by LPS and IFN‐γ attenuates the oxidative burst in macrophages
VON, K. A., & Brüne, B. (2001) · The FASEB Journal · doi:10.1096/fj.00-0187com · Cited by 75 · see citing works
Self-citationMendes, S. D. S., Candi, A., Vansteenbrugge, M., Pignon, M.-R., Bult, H., Boudjeltia, K. Z., Munaut, C., & Raes, M. J. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.02.025 · Cited by 62 · see citing works
PPAR‐γ: Therapeutic Potential for Multiple Sclerosis
Drew, P. D., Xu, J., & Racke, M. K. (2008) · PPAR Research · doi:10.1155/2008/627463 · Cited by 55 · see citing works
Zhou, M., Wu, R., Dong, W., Jacob, A., & Wang, P. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00340.2007 · Cited by 53 · see citing works
Kobayashi, M., Thomassen, M. J., Rambasek, T., Bonfield, T. L., Raychaudhuri, B., Malur, A., Winkler, A. R., Barna, B. P., Goldman, S. J., & Kavuru, M. S. (2005) · Annals of Allergy, Asthma & Immunology · doi:10.1016/s1081-1206(10)61173-8 · Cited by 37 · see citing works
The Regulation of Elongation by Eukaryotic RNA Polymerase II: A Recent View
Kim, D.-K., Yamaguchi, Y., Wada, T., & Handa, H. (2001) · Molecules and Cells · doi:10.1016/s1016-8478(23)17035-x · Cited by 22 · see citing works
Dushkin, M. I., Хощенко, О. М., Chasovsky, M. A., & Pivovarova, E. N. (2009) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-009-0505-3 · Cited by 10 · see citing works
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Zanger, U. M., & Schwab, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.12.007 · Cited by 4,169 · see citing works
“The same miRNA miR-27b also regulates the peroxisome proliferator-activated receptor PPARγ (Karbiener et al., 2009; Jennewein et al., 2010) and the liver X receptor (LXR) was shown to be regulated by miR-613 (Ou et al., 2011), further supporting an important role of miRNAs in hepatic gene…”
BackgroundMicroRNAs: the fine-tuners of Toll-like receptor signalling
O'Neill, L. A. J., Sheedy, F. J., & McCoy, C. E. (2011) · Nature reviews. Immunology · doi:10.1038/nri2957 · Cited by 851 · see citing works
Chhor, V., Charpentier, T. L., Lebon, S., Oré, M. V., Lara‐Celador, I., Josserand, J., Degos, V., Jacotot, E. D., Hagberg, H., Sävman, K., et al. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.02.005 · Cited by 647 · see citing works
Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS
Butovsky, O., Siddiqui, S., Gabriely, G., Lanser, A. J., Dake, B., Murugaiyan, G., Doykan, C. E., Wu, P. M., Gali, R. R., Iyer, L. K., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62636 · Cited by 481 · see citing works
Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23∼27∼24 clusters
Zhou, Q., Gallagher, R., Ufret-Vincenty, R., Li, X., Olson, E. N., & Wang, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105254108 · Cited by 341 · see citing works
MicroRNA in TLR signaling and endotoxin tolerance
Nahid, M. A., Satoh, M., & Chan, E. K. L. (2011) · Cellular and Molecular Immunology · doi:10.1038/cmi.2011.26 · Cited by 295 · see citing works
MicroRNAs: Roles in Regulating Neuroinflammation
Gaudet, A. D., Fonken, L. K., Watkins, L. R., Nelson, R. J., & Popovich, P. G. (2017) · The Neuroscientist · doi:10.1177/1073858417721150 · Cited by 270 · see citing works
MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction
Meder, B., Keller, A., Vogel, B., Haas, J., Sedaghat‐Hamedani, F., Kayvanpour, E., Just, S., Borries, A., Rudloff, J., Leidinger, P., et al. (2010) · Basic Research in Cardiology · doi:10.1007/s00395-010-0123-2 · Cited by 263 · see citing works
“Similarly, miR-27b, which directly targets and destabilizes peroxisome proliferator-activated receptorgamma (PPARc) mRNA [21], is also upregulated in the AMI group (24.”
BackgroundLactation-Related MicroRNA Expression Profiles of Porcine Breast Milk Exosomes
Gu, Y., Li, M., Wang, T., Liang, Y., Zhong, Z., Wang, X., Zhou, Q. G., Chen, L., Lang, Q., He, Z., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043691 · Cited by 261 · see citing works
“miR-27b-3p destabilizes the mRNA abundance of lipopolysaccharide-mediated PPARc (peroxisome proliferator-activated receptor c), which is often associated with chronic inflammatory diseases provoked by insufficient resolution of an immune response [33].”
BackgroundSu, S., Zhao, Q., He, C., Huang, D., Liu, J., Chen, F., Chen, J., Liao, J.-Y., Cui, X., Zeng, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms9523 · Cited by 253 · see citing works
MicroRNAs in Vascular and Metabolic Disease
Zampetaki, A., & Mayr, M. (2012) · Circulation Research · doi:10.1161/circresaha.111.247445 · Cited by 242 · see citing works
MicroRNAs: New Regulators of Toll-Like Receptor Signalling Pathways
He, X., Jing, Z., & Cheng, G. (2014) · BioMed Research International · doi:10.1155/2014/945169 · Cited by 238 · see citing works
Povero, D., Panera, N., Eguchi, A., Johnson, C. D., Papouchado, B. G., de Araujo Horcel, L., Pinatel, E. M., Alisi, A., Nobili, V., & Feldstein, A. E. (2015) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2015.07.007 · Cited by 221 · see citing works
“To investigatewhether hepatocytederived EVs induce a phenotypical switch from quiescent to activated HSCs by regulating PPAR-g expression, we exposed LX2 cells to Hep-EVs, and determined the mRNA and protein expression level of PPAR-g.”
BackgroundAlsaweed, M., Hartmann, P. E., Geddes, D. T., & Kakulas, F. (2015) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph121113981 · Cited by 223 · see citing works
Transcriptional Regulation of Macrophages Polarization by MicroRNAs
Li, H., Jiang, T., Li, M., Zheng, X., & Zhao, G.-J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01175 · Cited by 204 · see citing works
MicroRNA expression profiles of bovine milk exosomes in response to Staphylococcus aureus infection
Sun, J., Aswath, K., Schroeder, S., Lippolis, J. D., Reinhardt, T. A., & Sonstegard, T. S. (2015) · BMC Genomics · doi:10.1186/s12864-015-2044-9 · Cited by 203 · see citing works
“In the case of miR-27b, mRNA stability of PPARgamma is destabilized, which is often associated with chronic inflammatory diseases provoked by an immune response [51].”
BackgroundCardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice
Wang, J., Song, Y., Zhang, Y., Xiao, H., Sun, Q., Hou, N., Guo, S., Wang, Y., Fan, K., Zhan, D., et al. (2011) · Cell Research · doi:10.1038/cr.2011.132 · Cited by 203 · see citing works
Non-coding RNAs in cardiovascular cell biology and atherosclerosis
Fasolo, F., Gregoli, K. D., Mäegdefessel, L., & Johnson, J. L. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz203 · Cited by 202 · see citing works
Identification of miRNAs associated with the follicular–luteal transition in the ruminant ovary
McBride, D., Carré, W., Sontakke, S. D., Hogg, C. O., Law, A., Donadeu, F. X., & Clinton, M. (2012) · Reproduction · doi:10.1530/rep-12-0025 · Cited by 198 · see citing works
“…inflammation, innate immunity and angiogenesis (Chen et al. 2004, Otsuka et al. 2008, Yamakuchi et al. 2008, Liu et al. 2009, Guo et al. 2010, Jennewein et al. 2010, Kuhn et al. 2010, Sheedy et al. 2010, Caporali et al. 2011, Shatseva et al. 2011), all of which are intrinsically associated…”
BackgroundJin, W., Ibeagha-Awemu, E. M., Liang, G., et al. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-181 · Cited by 193 · see citing works
“Up-regulation of miR-27b by LPS was found to destabilize proliferator-activated receptor γ1 (PPARγ1) mRNA which is often associated with chronic inflammatory diseases [41].”
BackgroundSedighzadeh, S. S., Khoshbin, A. P., Razi, S., Keshavarz‐Fathi, M., & Rezaei, N. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-1241 · Cited by 188 · see citing works
Regulation of Cyclin T1 and HIV-1 Replication by MicroRNAs in Resting CD4 + T Lymphocytes
Chiang, K., Sung, T.-L., & Rice, A. P. (2011) · Journal of Virology · doi:10.1128/jvi.05065-11 · Cited by 180 · see citing works
Zhang, M., Wu, J., Chen, W., Tang, S., Mo, Z., Tang, Y., Li, Y., Wang, J., Liu, X., Peng, J., et al. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.02.008 · Cited by 177 · see citing works
Emerging role of microRNAs in lipid metabolism
Yang, Z., Cappello, T., & Wang, L. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.01.002 · Cited by 173 · see citing works
Lee, J.-J., Drakaki, A., Iliopoulos, D., & Struhl, K. (2011) · Oncogene · doi:10.1038/onc.2011.543 · Cited by 164 · see citing works
“The miR-27 family (miR-27a and miR-27b) directly targets PPARγ, and it inhibits adipocyte differentiation (Karbiener et al., 2009; Kim et al., 2010) and is induced upon inflammation in macrophages (Jennewein et al., 2010).”
BackgroundPPARα Is Regulated by miR-21 and miR-27b in Human Liver
Kida, K., Nakajima, M., Mohri, T., Oda, Y., Takagi, S., Fukami, T., & Yokoi, T. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0473-y · Cited by 126 · see citing works
“In addition, PPARγ (16), glucocorticoid receptor”
BackgroundMicroRNAs in the regulation of TLR and RIG-I pathways
Li, Y., & Shi, X. (2012) · Cellular and Molecular Immunology · doi:10.1038/cmi.2012.55 · Cited by 125 · see citing works
The magic and mystery of MicroRNA-27 in atherosclerosis
Chen, W., Yin, K., Zhao, G., Fu, Y., & Tang, C. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.01.020 · Cited by 120 · see citing works
The Emerging Role of Epigenetics in Inflammation and Immunometabolism
Raghuraman, S., Donkin, I., Versteyhe, S., Barrès, R., & Simar, D. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.06.008 · Cited by 117 · see citing works
Gu, C., Xu, Y., Zhang, S., Guan, H., Shi, S., Wang, X., Wang, Y., Li, Y., & Zhao, G. (2016) · Scientific Reports · doi:10.1038/srep38491 · Cited by 118 · see citing works
Lawless, N., Foroushani, A. B. K., McCabe, M. S., O’Farrelly, C., & Lynn, D. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057543 · Cited by 115 · see citing works
“ulator of the inflammatory response [43].”
MicroRNA regulation of innate immune responses in epithelial cells
Zhou, R., O’Hara, S. P., & Chen, X. (2011) · Cellular and Molecular Immunology · doi:10.1038/cmi.2011.19 · Cited by 111 · see citing works
microRNAs as Mediators of Drug Toxicity
Yokoi, T., & Nakajima, M. (2012) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140250 · Cited by 110 · see citing works
Tang, Y., Yang, L., Liu, H., Song, Y.-J., Yang, Q.-Q., Liu, Y., Qian, S., & Tang, Q. (2023) · Cell Reports · doi:10.1016/j.celrep.2022.111948 · Cited by 103 · see citing works
The involvement of microRNAs in Type 2 diabetes
Ferland-McCollough, D., Ozanne, S. E., Siddle, K., Willis, A. E., & Bushell, M. (2010) · Biochemical Society Transactions · doi:10.1042/bst0381565 · Cited by 98 · see citing works
The Nuclear Hormone Receptor PPARγas a Therapeutic Target in Major Diseases
Schmidt, M. V., Brüne, B., & von Knethen, A. (2010) · The Scientific World JOURNAL · doi:10.1100/tsw.2010.213 · Cited by 94 · see citing works
“treatment rapidly down-regulates PPAR after 6–15 h by miR27b-dependent mRNA destabilization[119], followed by its up-regulation again at later time points[120,121].”
BackgroundSelf-citationCordani, N., Pisa, V., Pozzi, L., Sciorati, C., & Clementi, E. (2013) · Stem Cells · doi:10.1002/stem.1587 · Cited by 90 · see citing works
Cardiovascular Importance of the MicroRNA‐23/27/24 Family
BANG, C., FIEDLER, J., & THUM, T. (2012) · Microcirculation · doi:10.1111/j.1549-8719.2011.00153.x · Cited by 90 · see citing works
Neuroinflammation and Its Impact on the Pathogenesis of COVID-19
Almutairi, M. M., Sivandzade, F., Albekairi, T. H., Alqahtani, F., & Cucullo, L. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.745789 · Cited by 88 · see citing works
Fu, S.-P., Chen, S., Pang, Q.-M., Zhang, M., Wu, X.-C., Wan, X., Wan, W.-H., Ao, J., & Zhang, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1014013 · Cited by 89 · see citing works
Toxicological Implications of Modulation of Gene Expression by MicroRNAs
Yokoi, T., & Nakajima, M. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr168 · Cited by 83 · see citing works
Early Life Stress and Epigenetics in Late-onset Alzheimer’s Dementia: A Systematic Review
Lemche, E. (2018) · Current Genomics · doi:10.2174/1389202919666171229145156 · Cited by 82 · see citing works
miR-15a/16 Regulates Macrophage Phagocytosis after Bacterial Infection
Moon, H.-G., Yang, J., Zheng, Y., & Jin, Y. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401372 · Cited by 81 · see citing works
Extrahepatic metabolism at the body's internal–external interfaces
Gundert‐Remy, U., Bernauer, U., Blömeke, B., Döring, B., Fabian, E. J., Goebel, C., Hessel‐Pras, S., Jäckh, C., Lampen, A., Oesch, F., et al. (2014) · Drug Metabolism Reviews · doi:10.3109/03602532.2014.900565 · Cited by 82 · see citing works
“CYP2E1 expression is regulated by miR-378 (Mohri et al., 2010). miR-27b has further regulating activity at the peroxisome proliferator-activated receptor PPARg (Jennewein et al., 2010; Karbiener et al., 2009).”
BackgroundDai, L., Tsai‐Morris, C., Satô, H., Villar, J., Kang, J., Zhang, J., & Dufau, M. L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.282756 · Cited by 75 · see citing works
Zhou, J.-H., Zhou, Q.-Z., Lyu, X., et al. (2014) · Biology of Reproduction · doi:10.1095/biolreprod.114.124487 · Cited by 73 · see citing works
“It also inhibits the inflammatory response [73, 74], angiogenesis [75], as well as impairs adipogenesis [76] and mitochondrial function [77].”
BackgroundXu, S., Hu, H.-T., Li, H. L., & Chang, S. (2019) · Cells · doi:10.3390/cells8101140 · Cited by 72 · see citing works
“mmu-miR-126 [19](+) hsa-miR-125a/b-5p [40] mmu-miR-125a-3p [31,44] mmu- miR-125b [45] hsa-miR-181a [46] mmu-miR-181a [46] mmu-miR-23a/b-5p [31] hsa-miR-27b [47] mmu-miR-27a [48] hsa-miR-3614-5p [49](–)”
MicroRNAs-Dependent Regulation of PPARs in Metabolic Diseases and Cancers
Portius, D., Sobolewski, C., & Foti, M. (2017) · PPAR Research · doi:10.1155/2017/7058424 · Cited by 71 · see citing works
Noncoding microRNAs: small RNAs play a big role in regulation of ADME?
Yu, A., & Pan, Y. (2012) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2012.02.011 · Cited by 69 · see citing works
Kim, Y. J., Ku, S., Kim, Y. Y., et al. (2013) · Human Reproduction · doi:10.1093/humrep/det338 · Cited by 69 · see citing works
Lv, Y., Ouyang, A., & Fu, L. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0361-4 · Cited by 66 · see citing works
“…2 (TICAM-2) (Li et al. 2015), MCP-1-induced protein 1 (MCPIP1) (Cheng et al. 2015), secreted frizzled-related protein 1 (SFRP1) (Wang et al. 2015), dihydropyrimidine dehydrogenase (DPD) (Hirota et al. 2012), and peroxisome proliferator-activated receptor gamma (PPAR c) (Jennewein et al. 2010).”
miRNAs as potential therapeutic targets for age-related macular degeneration
Wang, S., Koster, K. M., He, Y., & Zhou, Q. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.11.176 · Cited by 67 · see citing works
Overexpression of gankyrin induces liver steatosis in zebrafish (Danio rerio)
Her, G. M., Hsu, C.-C., Hong, J., et al. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.06.011 · Cited by 67 · see citing works
Zhao, G.-J., Tang, S., Lv, Y.-C., Ouyang, X.-P., He, P., Yao, F., Chen, W., Lu, Q., Tang, Y., Zhang, M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074782 · Cited by 66 · see citing works
PPARs in Liver Diseases and Cancer: Epigenetic Regulation by MicroRNAs
Peyrou, M., Ramadori, P., Bourgoin, L., & Foti, M. (2012) · PPAR Research · doi:10.1155/2012/757803 · Cited by 65 · see citing works
“For example, downregulation of PPARγ by an aberrant expression of miR-27b in cardiomyocytes was associated with cardiac hypertrophy in mice [170], whereas miR-27b-dependent PPARγ downregulation in macrophages favors the inflammatory response to LPS [171].”
BackgroundMicroRNAs associated with the pathogenesis of multiple sclerosis
Huang, Q., Xiao, B., Ma, X., Qu, M., Li, Y., Nagarkatti, P. S., Nagarkatti, M., & Zhou, J. (2016) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2016.04.014 · Cited by 65 · see citing works
“expression (Jennewein et al., 2010).”
Boß, M., Kemmerer, M., Brüne, B., & Namgaladze, D. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.03.042 · Cited by 65 · see citing works
Self-citationPharmacokinetics, Pharmacodynamics, and Side Effects of Midazolam: A Review and Case Example
Peter, J., Dieudonné, P., & Zolk, O. (2024) · Pharmaceuticals · doi:10.3390/ph17040473 · Cited by 71 · see citing works
Nakajima, M., & Yokoi, T. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.04.009 · Cited by 64 · see citing works
“4.3 Others Several research groups (Karbiener et al., 2009; Lin et al., 2009; Jennewein et al., 2010; Kim et al., 2010) have reported that miR-27a and miR-27b repress the expression of peroxisome proliferator-activated receptor γ (PPARγ) suggesting an association with the change in adipocyte…”
BackgroundInfluentialTherapeutic manipulation of angiogenesis with miR-27b
Veliceasa, D., Biyashev, D., Qin, G., Misener, S., Mackie, A. R., Kishore, R., & Volpert, O. V. (2015) · Vascular Cell · doi:10.1186/s13221-015-0031-1 · Cited by 63 · see citing works
“miR-27b was previously implicated in the regulation of macrophage responses [39].”
BackgroundInfluentialMicroRNA regulation of macrophages in human pathologies
Wei, Y., & Schober, A. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2254-6 · Cited by 63 · see citing works
“Up- and downregulation of miR-27a/b-3p expression by LPS treatment has been reported in human macrophages [111, 253], whereas IL-4 increases and LPS reduces miR-27-3p expression in mouse macrophages [171, 254, 255].”
Rastogi, N., Gara, R. K., Trivedi, R., et al. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.12.016 · Cited by 62 · see citing works
Hou, X., Tian, J., Geng, J., Xiao, L., Tang, X., Zhang, J., & Bai, X. (2016) · Oncotarget · doi:10.18632/oncotarget.10283 · Cited by 61 · see citing works
Hypoxia Mediates Mutual Repression between microRNA-27a and PPARγ in the Pulmonary Vasculature
Kang, B., Park, K. K., Green, D. E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079503 · Cited by 61 · see citing works
“First, the 39untranslated region (39UTR) of PPARc contains a binding site for miR-27, and miR-27 targets PPARcmRNA in cardiomyocytes [34] and macrophages [35].”
BackgroundNMDA Mediated Contextual Conditioning Changes miRNA Expression
Kye, M. J., Neveu, P. A., Lee, Y., Zhou, M., Steen, J. A. J., Şahin, M., Kosik, K. S., & Silva, A. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024682 · Cited by 58 · see citing works
Zhang, S., Liu, F., Mao, X., et al. (2015) · International Journal of Oncology · doi:10.3892/ijo.2015.3162 · Cited by 57 · see citing works
miR‐130b‐3p regulates M1 macrophage polarization via targeting IRF1
Guo, Q., Zhu, X., Wei, R., Zhao, L., Zhang, Z., Yin, X., Zhang, Y., Chu, C., Wang, B., & Li, X. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.29987 · Cited by 54 · see citing works
Vascular PPARδ Protects Against Stroke-Induced Brain Injury
Yin, K., Deng, Z., Hamblin, M., Zhang, J., & Chen, Y. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.221267 · Cited by 52 · see citing works
Zhang, Q., Huang, F., Yao, Y., Wang, J., Wei, J., Wu, Q., Xiang, S., & Xu, L. (2019) · Cancer Science · doi:10.1111/cas.14101 · Cited by 52 · see citing works
PPARs: Protectors or Opponents of Myocardial Function?
Pol, C. J., Lieu, M., & Drosatos, K. (2015) · PPAR Research · doi:10.1155/2015/835985 · Cited by 50 · see citing works
Sato, H., Sugai, H., Kurosaki, H., Ishikawa, M., Funaki, A., Kimura, Y., & Ueno, K. (2013) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b12-00868 · Cited by 47 · see citing works
Dou, X., Xiao, J., Jin, Z., et al. (2015) · Oncology Letters · doi:10.3892/ol.2015.3397 · Cited by 47 · see citing works
“Previous studies have found that during the process of LPS-stimulated downregulation of PPAR-γ, the half-life of the PPAR-γ mRNA was shortened, and small non-coding RNA, termed microRNA, may be involved in this process (35).”
BackgroundBi, R., Bao, C., Lianyong, J., et al. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.03.057 · Cited by 45 · see citing works
MicroRNAs in the Host-Apicomplexan Parasites Interactions: A Review of Immunopathological Aspects
Judice, C. C., Bourgard, C., Kayano, A. C. A. V., Albrecht, L., & Costa, F. T. M. (2016) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2016.00005 · Cited by 46 · see citing works
Macrophage/foam cell is an attribute of inflammation: Mechanisms of formation and functional role
Dushkin, M. I. (2012) · Biochemistry (Moscow) · doi:10.1134/s0006297912040025 · Cited by 44 · see citing works
A meta-analysis of microRNA expression profiling studies in heart failure
Gholaminejad, A., Zare, N., Dana, N., Shafie, D., Mani, A., & Javanmard, S. H. (2021) · Heart Failure Reviews · doi:10.1007/s10741-020-10071-9 · Cited by 44 · see citing works
“ACE2 angiotensin-convertingenzyme2; Bcl-2 B cell lymphoma-2; NFATC4 nuclear factor of activated T cells; CTGF connective tissue growth factor; MMP-1 matrix metalloproteinase-1; TGF-β transforming growth factor-β; PDCD4 programmed cell death 4; SP1 specific protein 1; PTEN phosphatase and tensin homolog deleted on chro…”
BackgroundInfluentialKalliora, C., & Drosatos, K. (2020) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000891 · Cited by 43 · see citing works
Nasrabadi, P. N., Zareian, S., Nayeri, Z., Salmanipour, R., Parsafar, S., Gharib, E., Aghdaei, H. A., & Zali, M. R. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28204 · Cited by 43 · see citing works
Kumar, D., Sahoo, S. S., Chauss, D., Kazemian, M., & Afzali, B. (2022) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102982 · Cited by 42 · see citing works
Aging and serum exomiR content in women-effects of estrogenic hormone replacement therapy
Kangas, R., Törmäkangas, T., Fey, V., Pursiheimo, J., Miinalainen, I., Alén, M., Kaprio, J. A., Sipilä, S., Säämänen, A., Kovanen, V., et al. (2017) · Scientific Reports · doi:10.1038/srep42702 · Cited by 41 · see citing works
Xu, Y., Han, Y., Ye, B., et al. (2018) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13076 · Cited by 41 · see citing works
Plasma microRNA vary in association with the progression of Alzheimer's disease
Guévremont, D., Tsui, H., Knight, R. G., Fowler, C. J., Masters, C. L., Martins, R. N., Abraham, W. C., Tate, W. P., Cutfield, N. J., & Williams, J. M. (2022) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12251 · Cited by 41 · see citing works
Cho, S., Kook, M., Lee, J. H., Shin, J., Park, J., Bae, Y., Choi, I. J., Ryu, K. W., & Kim, Y. (2014) · International Journal of Cancer · doi:10.1002/ijc.29056 · Cited by 41 · see citing works
Insulin Resistance Associated Genes and miRNAs
Honardoost, M., Sarookhani, M. R., Arefian, E., & Soleimani, M. (2014) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-014-1014-z · Cited by 40 · see citing works
Xie, H., Hu, J.-L., Li, J., et al. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.05.024 · Cited by 40 · see citing works
Izzotti, A., Larghero, P., Balansky, R. M., Pfeffer, U., Steele, V. E., & Flora, S. D. (2010) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2010.10.003 · Cited by 39 · see citing works
van Harten, A. C., Mulders, J., Scheltens, P., van der Flier, W. M., & Oudejans, C. B. M. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-140075 · Cited by 41 · see citing works
MicroRNA regulation of the major drug-metabolizing enzymes and related transcription factors
Dluzen, D. F., & Lazarus, P. J. (2015) · Drug Metabolism Reviews · doi:10.3109/03602532.2015.1076438 · Cited by 38 · see citing works
“Members of the miR-27 family, miR-27a and 27b, both regulate PPARg which may have implications in adipocyte regulation and inflammation (Jennewein et al., 2010; Kim et al., 2010). miR-27b has also been found to regulate PPARg in vitro and in mice.”
Contribution of MicroRNA ‐27b‐3p to Synovial Fibrotic Responses in Knee Osteoarthritis
Tavallaee, G., Lively, S. S., Rockel, J. S., Ali, S. A., Im, M., Sarda, C., Mitchell, G. M., Rossomacha, E., Nakamura, S., Potla, P., et al. (2022) · Arthritis & Rheumatology · doi:10.1002/art.42285 · Cited by 38 · see citing works
“When the top predicted transcription factors of ADAMTS8 and miR-27b-3p targets were examined and cross-referenced, PPARG was the only one identified by RNA sequencing to be down-regulated by miR-27b-3p transfection of OA FLS. PPARG, a previously identified target of miR-27b-3p (49,50) with a miR-27b–targeted sequence…”
BackgroundLewkowicz, P., Ćwiklińska, H., Mycko, M. P., Cichalewska, M., Domowicz, M., Lewkowicz, N., Jurewicz, A., & Selmaj, K. W. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4794-14.2015 · Cited by 37 · see citing works
“Based on some initial studies, it has also been proposed that a genetic association of miRNA and inflammatory pathology might also exist (Jennewein et al., 2010), but these data are limited in regard to inflammatory disorders.”
Backgroundmi R ‐27 impairs the adipogenic lineage commitment via targeting lysyl oxidase
Chen, S., Xu, X., Ning, L., Jiang, W., Xing, C., Tang, Q., & Huang, H. (2015) · Obesity · doi:10.1002/oby.21319 · Cited by 37 · see citing works
Hu, Y.-H., Han, J. H., Wang, L., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.692806 · Cited by 36 · see citing works
“However, this attempt may fail under intense in fl ammation, because their mRNA can be destabilized (Jennewein et al., 2010; Zhang et al., 2019).”
Vicinus, B., Rubie, C., Faust, S. K., Frick, V. O., Ghadjar, P., Wagner, M., Graeber, S. M., & Schilling, M. K. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.10.031 · Cited by 35 · see citing works
ncRNA-regulated immune response and its role in inflammatory lung diseases
Xie, N., & Liu, G. (2015) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00286.2015 · Cited by 36 · see citing works
Fucci, A., Colangelo, T., Votino, C., et al. (2012) · PPAR Research · doi:10.1155/2012/242498 · Cited by 35 · see citing works
“In addition, miR-27 reduces PPARγ expression in LPS-stimulated macrophages, inhibiting its anti-inflammatory activity [92].”
BackgroundBedi, B., Maurice, N. M., Ciavatta, V. T., Lynn, K. S., Yuan, Z., Molina, S. A., Joo, M., Tyor, W. R., Goldberg, J. B., Koval, M. H., et al. (2017) · The FASEB Journal · doi:10.1096/fj.201700075r · Cited by 35 · see citing works
“PTMs of the PAPRg mRNA transcript can also be mediated by microRNAs (64).”
BackgroundMicroRNAs as regulators of mitochondrial dysfunction and obesity
Murri, M., & el Azzouzi, H. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00691.2017 · Cited by 34 · see citing works
The effects of micro RNA on the absorption, distribution, metabolism and excretion of drugs
He, Y., Chevillet, J. R., Liu, G., Kim, T. K., & Wang, K. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12968 · Cited by 33 · see citing works
“…miR-10b, -506, -21, -27b Zheng et al., 2010; Kida et al., 2011; Tong et al., 2011; Zhou et al., 2011 NR1C3 Nuclear Receptor miR-130, -27b, -27a Jennewein et al., 2010; Kim et al., 2010; Lee et al., 2012 NR1C2 Nuclear Receptor miR-15a, -199a, -214, -9 Yin et al., 2010; el Azzouzi et al.,…”
Puttabyatappa, M., VandeVoort, C. A., & Chaffin, C. L. (2010) · Endocrinology · doi:10.1210/en.2010-0698 · Cited by 33 · see citing works
Xeno-miRNA in Maternal-Infant Immune Crosstalk: An Aid to Disease Alleviation
Stephen, B. J., Pareek, N., Saeed, M., Kausar, M. A., Rahman, S., & Datta, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00404 · Cited by 31 · see citing works
- Authors
- Jennewein, C., von Knethen, A., Schmid, T., & Brüne, B.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Brüne, Bernhard
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 285
- Issue
- 16
- Pages
- 11846-11853
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2852921
- OpenAlex
- W2023869046
- Cited by
- 183
- References
- 46
- Citations by year
- 2025: 2 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 12 · 2020: 5 · 2019: 10 · 2018: 10 · 2017: 16 · 2016: 16 · 2015: 19 · 2014: 16 · 2013: 14 · 2012: 16
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- microRNA-27b, PPARγ1, mRNA stability, lipopolysaccharide, macrophages, 3' untranslated region, microRNA binding sites, inflammation, inflammatory cytokines, TNF-α, interleukin-6, chronic inflammatory diseases
- MeSH terms
- Base Sequence, Binding Sites, Cells, Cultured, Humans, Lipopolysaccharides, Macrophages, Molecular Sequence Data, Mutation, RNA, Messenger, Transfection, Tumor Necrosis Factor-alpha, Interleukin-6, Sequence Deletion, DNA Primers, 3' Untranslated Regions, RNA Stability, MicroRNAs, PPAR gamma
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