CoChat
Sign Up
Cited by 11MicroRNA in disease regulationSepsis Diagnosis and TreatmentInflammation biomarkers and pathways

MicroRNA-23a reduces lipopolysaccharide-induced cellular apoptosis and inflammatory cytokine production through Rho-associated kinase 1/sirtuin-1/nuclear factor-kappa B crosstalk

Open access
Shi, Xiao-Jun, Jin, Ye, Xu, Wei-Ming, Shen, Qing, Li, Jun, Chen, Kang·2021·Chinese Medical Journal
DOI 10.1097/cm9.0000000000001369PMC PMC8104237
Open this paper in CoChat — free account

Abstract

Background: MicroRNAs are closely associated with the progression and outcomes of multiple human diseases, including sepsis. In this study, we examined the role of miR-23a in septic injury. Methods: Lipopolysaccharide (LPS) was used to induce sepsis in a rat model and H9C2 and HK-2 cells. miR-23a expression was evaluated in rat myocardial and kidney tissues, as well as H9C2 and HK-2 cells. A miR-23a mimic was introduced into cells to identify the role of miR-23a in cell viability, apoptosis, and the secretion of inflammatory cytokines. Furthermore, the effect of Rho-associated kinase 1 (ROCK1), a miR-23a target, on cell damage was evaluated, and molecules involved in the underlying mechanism were identified. Results: In the rat model, miR-23a was poorly expressed in myocardial (sham vs. sepsis 1.00 ± 0.06 vs. 0.27 ± 0.03, P < 0.01) and kidney tissues (sham vs. sepsis 0.27 ± 0.03 vs. 1.00 ± 0.06, P < 0.01). Artificial overexpression of miR-23a resulted in increased proliferative activity (DNA replication rate: Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 34.13 ± 3.12 vs. 12.94 ± 1.21 vs. 13.31 ± 1.43 vs. 22.94 ± 2.26, P < 0.05; HK-2 cells: 15.17 ± 1.43 vs. 34.52 ± 3.46 vs. 35.19 ± 3.12 vs. 19.87 ± 1.52, P < 0.05), decreased cell apoptosis (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 11.39 ± 1.04 vs. 32.57 ± 2.29 vs. 33.08 ± 3.12 vs. 21.63 ± 2.35, P < 0.05; HK-2 cells: 15.17 ± 1.43 vs. 34.52 ± 3.46 vs. 35.19 ± 3.12 vs. 19.87 ± 1.52, P < 0.05), and decreased production of inflammatory cytokines, including interleukin-6 (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 59.61 ± 5.14 vs. 113.54 ± 12.30 vs. 116.51 ± 10.69 vs. 87.69 ± 2.97 ng/mL; P < 0.05, F = 12.67, HK-2 cells: 68.12 ± 6.44 vs. 139.65 ± 16.62 vs. 143.51 ± 13.64 vs. 100.82 ± 9.74 ng/mL, P < 0.05, F = 9.83) and tumor necrosis factor-α (Control vs. LPS vs. LPS + Mock vs. LPS + miR-23a: H9C2 cells: 103.20 ± 10.31 vs. 169.67 ± 18.84 vs. 173.61 ± 15.91 vs. 133.36 ± 12.32 ng/mL, P < 0.05, F = 12.67, HK-2 cells: 132.51 ± 13.37 vs. 187.47 ± 16.74 vs. 143.51 ± 13.64 vs. 155.79 ± 15.31 ng/mL, P < 0.05, F = 9.83) in cells. However, ROCK1 was identified as a miR-23a target, and further up-regulation of ROCK1 mitigated the protective function of miR-23a in LPS-treated H9C2 and HK-2 cells. Moreover, ROCK1 suppressed sirtuin-1 (SIRT1) expression to promote the phosphorylation of nuclear factor-kappa B (NF-κB) p65, indicating the possible involvement of this signaling pathway in miR-23a-mediated events. Conclusion: Our results indicate that miR-23a could suppress LPS-induced cell damage and inflammatory cytokine secretion by binding to ROCK1, mediated through the potential participation of the SIRT1/NF-κB signaling pathway.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1097/cm9.0000000000001369

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • miR-23a can alleviate lipopolysaccharide-induced cell damage by directly binding ROCK1 to inhibit its expression; ROCK1 prevents SIRT1 expression and stimulates NF-κB phosphorylation, thereby inhibiting lipopolysaccharide-induced cell damage and inflammatory cytokine secretion.

    “as well as by directly binding Rho associated coiled-coil containing protein kinase 1 (ROCK1) to inhibit its expression level. ROCK1 prevents the expression of SIRT1 and stimulates the phosphorylation of the NF-κB signaling pathway, thereby inhibiting lipopolysaccharide-induced cell damage and inflammatory cytokine secretion [38].”

    From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [38]

    Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 35 · Cited by 11

Research works printed but not linked: 34

  1. [1]Dickson K Lehmann C. Inflammatory response to different toxins in experimental sepsis models. Int J Mol Sci 2019; 20: 4341 doi: 10.3390/ijms20184341. PMC6770119 31491842 · DOI
  2. [2]Brown RM Semler MW. Fluid management in sepsis. J Intensive Care Med 2019; 34: 364– 373. doi: 10.1177/0885066618784861. 29986619 PMC6532631 · DOI
  3. [3]Stanzani G Duchen MR Singer M. The role of mitochondria in sepsis-induced cardiomyopathy. Biochim Biophys Acta Mol Basis Dis 2019; 1865: 759– 773. doi: 10.1016/j.bbadis.2018.10.011. 30342158 · DOI
  4. [4]Fani F Regolisti G Delsante M Cantaluppi V Castellano G Gesualdo L. Recent advances in the pathogenetic mechanisms of sepsis-associated acute kidney injury. J Nephrol 2018; 31: 351– 359. doi: 10.1007/s40620-017-0452-4. 29273917 · DOI
  5. [5]Thompson K Venkatesh B Finfer S. Sepsis and septic shock: current approaches to management. Intern Med J 2019; 49: 160– 170. doi: 10.1111/imj.14199. 30754087 · DOI
  6. [6]Benz F Roy S Trautwein C Roderburg C Luedde T. Circulating microRNAs as biomarkers for sepsis. Int J Mol Sci 2016; 17: 78 doi: 10.3390/ijms17010078. PMC4730322 26761003 · DOI
  7. [7]Kingsley SMK Bhat BV. Role of microRNAs in sepsis. Inflamm Res 2017; 66: 553– 569. doi: 10.1007/s00011-017-1031-9. 28258291 · DOI
  8. [8]Fu D Dong J Li P Tang C Cheng W Xu Z. miRNA-21 has effects to protect kidney injury induced by sepsis. Biomed Pharmacother 2017; 94: 1138– 1144. doi: 10.1016/j.biopha.2017.07.098. 28821165 · DOI
  9. [9]Ge C Liu J Dong S. miRNA-214 Protects sepsis-induced myocardial injury. Shock 2018; 50: 112– 118. doi: 10.1097/SHK.0000000000000978. 28858140 · DOI
  10. [10]Cui M Yao X Lin Y Zhang D Cui R Zhang X. Interactive functions of microRNAs in the miR-23a-27a-24-2 cluster and the potential for targeted therapy in cancer. J Cell Physiol 2020; 235: 6– 16. doi: 10.1002/jcp.28958. 31192453 · DOI
  11. [11]Bukauskas T Mickus R Cereskevicius D Macas A. Value of serum miR-23a, miR-30d, and miR-146a biomarkers in ST-elevation myocardial infarction. Med Sci Monit 2019; 25: 3925– 3932. doi: 10.12659/MSM.913743. 31130720 PMC6556071 · DOI
  12. [12]Xie W Chen L Chen L Kou Q. Silencing of long non-coding RNA MALAT1 suppresses inflammation in septic mice: role of microRNA-23a in the down-regulation of MCEMP1 expression. Inflamm Res 2020; 69: 179– 190. doi: 10.1007/s00011-019-01306-z. 31893303 · DOI
  13. [13]Yang J Mao M Zhen YY. miRNA-23a has effects to improve lung injury induced by sepsis in vitro and vivo study. Biomed Pharmacother 2018; 107: 81– 89. doi: 10.1016/j.biopha.2018.07.097. 30081205 · DOI · Paper page
  14. [14]Gong J Guan L Tian P Li C Zhang Y. Rho kinase type 1 (ROCK1) promotes lipopolysaccharide-induced inflammation in corneal epithelial cells by activating toll-like receptor 4 (TLR4)-mediated signaling. Med Sci Monit 2018; 24: 3514– 3523. doi: 10.12659/MSM.907277. 29804125 PMC5999052 · DOI
  15. [15]Meng L Cao H Wan C Jiang L. miR-539-5p alleviates sepsis-induced acute lung injury by targeting ROCK1. Folia Histochem Cytobiol 2019; 57: 168– 178. doi: 10.5603/FHC.a2019.0019. 31825519 · DOI
  16. [17]Chen C Cai C Lin H Zhang W Peng Y Wu K. Baicalein protects renal tubular epithelial cells against hypoxia-reoxygenation injury. Ren Fail 2018; 40: 603– 610. doi: 10.1080/0886022X.2018.1532910. 30384801 PMC6225411 · DOI
  17. [18]Mao SY Meng XY Xu ZW Zhang WC Jin XH Chen X. The role of ZFP580, a novel zinc finger protein, in TGF-mediated cytoprotection against chemical hypoxia-induced apoptosis in H9c2 cardiac myocytes. Mol Med Rep 2017; 15: 2154– 2162. doi: 10.3892/mmr.2017.6236. 28259939 PMC5364886 · DOI
  18. [19]de Mingo A de Gregorio E Moles A Tarrats N Tutusaus A Colell A. Cysteine cathepsins control hepatic NF-kappaB-dependent inflammation via sirtuin-1 regulation. Cell Death Dis 2016; 7: e2464 doi: 10.1038/cddis.2016.368. 27831566 PMC5260902 · DOI
  19. [20]Liu Q Zhao H Gao Y Meng Y Zhao XX Pan SN. Effects of dandelion extract on the proliferation of rat skeletal muscle cells and the inhibition of a lipopolysaccharide-induced inflammatory reaction. Chin Med J 2018; 131: 1724– 1731. doi: 10.4103/0366-6999.235878. 29998893 PMC6048917 · DOI
  20. [21]Balija TM Lowry SF. Lipopolysaccharide and sepsis-associated myocardial dysfunction. Curr Opin Infect Dis 2011; 24: 248– 253. doi: 10.1097/QCO.0b013e32834536ce. 21378563 · DOI
  21. [22]Obonyo NG Fanning JP Ng AS Pimenta LP Shekar K Platts DG. Effects of volume resuscitation on the microcirculation in animal models of lipopolysaccharide sepsis: a systematic review. Intensive Care Med Exp 2016; 4: 38 doi: 10.1186/s40635-016-0112-3. 27873263 PMC5118377 · DOI
  22. [23]Wang Y Zhang L Zhao X Yang W Zhang R. An experimental study of the protective effect of simvastatin on sepsis-induced myocardial depression in rats. Biomed Pharmacother 2017; 94: 705– 711. doi: 10.1016/j.biopha.2017.07.105. 28800541 · DOI
  23. [24]Xu J Lin C Wang T Zhang P Liu Z Lu C. Ergosterol attenuates LPS-induced myocardial injury by modulating oxidative stress and apoptosis in rats. Cell Physiol Biochem 2018; 48: 583– 592. doi: 10.1159/000491887. 30021198 · DOI
  24. [25]Zhu Y Fu Y Lin H. Baicalin inhibits renal cell apoptosis and protects against acute kidney injury in pediatric sepsis. Med Sci Monit 2016; 22: 5109– 5115. doi: 10.12659/msm.899061. 28013315 PMC5207012 · DOI
  25. [26]Fang Y Xu XY Shen Y Li J. miR-23a-3p and miR-23a-5p target CiGadd45ab to modulate inflammatory response and apoptosis in grass carp. Fish Shellfish Immunol 2020; 98: 34– 44. doi: 10.1016/j.fsi.2019.12.076. 31883472 · DOI
  26. [27]Hu J Zhai C Hu J Li Z Fei H Wang Z. miR-23a inhibited IL-17-mediated proinflammatory mediators expression via targeting IKKalpha in articular chondrocytes. Int Immunopharmacol 2017; 43: 1– 6. doi: 10.1016/j.intimp.2016.11.031. 27936459 · DOI
  27. [28]Li Z Xu R Zhu X Li Y Wang Y Xu W. MicroRNA-23a-3p improves traumatic brain injury through modulating the neurological apoptosis and inflammation response in mice. Cell Cycle 2020; 19: 24– 38. doi: 10.1080/15384101.2019.1691763. 31818176 PMC6927724 · DOI
  28. [29]Mong PY Wang Q. Activation of Rho kinase isoforms in lung endothelial cells during inflammation. J Immunol 2009; 182: 2385– 2394. doi: 10.4049/jimmunol.0802811. 19201893 · DOI
  29. [30]Siddiqui MR Akhtar S Shahid M Tauseef M McDonough K Shanley TP. miR-144-mediated Inhibition of ROCK1 protects against LPS-induced lung endothelial hyperpermeability. Am J Respir Cell Mol Biol 2019; 61: 257– 265. doi: 10.1165/rcmb.2018-0235OC. 30811958 · DOI
  30. [31]Zhang J Yang GM Zhu Y Peng XY Li T Liu LM. Role of connexin 43 in vascular hyperpermeability and relationship to Rock1-MLC20 pathway in septic rats. Am J Physiol Lung Cell Mol Physiol 2015; 309: L1323– L1332. doi: 10.1152/ajplung.00016.2015. 26342084 · DOI
  31. [32]Lan KC Chao SC Wu HY Chiang CL Wang CC Liu SH. Salidroside ameliorates sepsis-induced acute lung injury and mortality via downregulating NF-kappaB and HMGB1 pathways through the upregulation of SIRT1. Sci Rep 2017; 7: 12026 doi: 10.1038/s41598-017-12285-8. 28931916 PMC5607272 · DOI
  32. [33]Zhuo Y Zhang S Li C Yang L Gao H Wang X. Resolvin D1 promotes SIRT1 expression to counteract the activation of STAT3 and NF-kappaB in mice with septic-associated lung injury. Inflammation 2018; 41: 1762– 1771. doi: 10.1007/s10753-018-0819-2. 30014231 · DOI
  33. [34]Savran M Aslankoc R Ozmen O Erzurumlu Y Savas HB Temel EN. Agomelatine could prevent brain and cerebellum injury against LPS-induced neuroinflammation in rats. Cytokine 2020; 127: 154957 doi: 10.1016/j.cyto.2019.154957. 31869757 · DOI
  34. [35]Xie MY Hou LJ Sun JJ Zeng B Xi QY Luo JY. Porcine milk exosome miRNAs attenuate LPS-induced apoptosis through inhibiting TLR4/NF-kappaB and p53 pathways in intestinal epithelial cells. J Agric Food Chem 2019; 67: 9477– 9491. doi: 10.1021/acs.jafc.9b02925. 31429552 · DOI

Authors
Shi, X.-J., Jin, Y., Xu, W.-M., Shen, Q., Li, J., & Chen, K.
Affiliations
Shanghai Jiao Tong University (CN)
ORCID
Chen, Kang
Venue
Chinese Medical Journal
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-02-03
Volume
134
Issue
7
Pages
829-839
ISSN
  • 0366-6999 (ISSN-L)
  • 2542-5641
DOI
10.1097/cm9.0000000000001369
PMC
PMC8104237
OpenAlex
W3128445896
Cited by
11
References
35
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 2
FWCI
0.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Chinese Medical Journal (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords
miR-23a, SIRT1, NF-κB, lipopolysaccharide, sepsis, apoptosis, inflammatory cytokines, cardiomyocytes, renal tubular epithelial cells, septic cardiomyopathy, sepsis-associated acute kidney injury
MeSH terms
Animals, Cell Line, Inflammation, Lipopolysaccharides, Cytokines, NF-kappa B, Apoptosis, MicroRNAs, Rats, rho-Associated Kinases, Sirtuin 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review