The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index; 18 of the 68 sources its claims cite were checked for support.
STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration
Open accessAbstract
STAT3 is rapidly induced during liver regeneration in an interleukin 6 (IL-6)-dependent fashion, and IL-6 is required for normal liver regeneration. We wanted to know whether STAT3 was also required for liver regeneration but disruption of the STAT3 gene during embryonic stages causes lethality. Therefore, an albumin promoter-driven Cre-loxP recombination system was used to create a STAT3 deletion in the adult mouse liver to study the role of STAT3 in liver regeneration. After partial hepatectomy, there was virtually no STAT3 RNA or protein induction in Alb(+) STAT3(fl/fl) livers. STAT3 DNA binding activity was also absent in Alb(+) STAT3(fl/fl) livers. Unlike in control livers, STAT1 was activated in STAT3 conditional-mutant livers posthepatectomy. Hepatocyte DNA synthesis at 40 h posthepatectomy in Alb(+) STAT3(fl/fl) livers was reduced to approximately one-third of the control. Alb(+) STAT3(fl/fl) livers had abnormalities in immediate-early gene activation that largely correlated with but were not identical to those seen in IL-6-/- livers. G(1) phase cyclins including cyclins D1 and E had lower expression levels in Alb(+) STAT3(fl/fl) livers, indicating an abnormal G(1) to S phase transition. Therefore, STAT3 accounts for part of the DNA synthetic response of the hepatocytes during liver regeneration, which cannot be compensated for by induction of STAT1. Normal activation of the MAPK pathway in Alb(+) STAT3(fl/fl) livers reinforces the fact that at least part of the effect of IL-6 on hepatocyte proliferation is not mediated by STAT3. This study provides the first in vivo evidence that STAT3 promotes cell cycle progression and cell proliferation under physiological growth conditions.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Using an albumin promoter–driven Cre-loxP system to delete STAT3 in adult mouse liver, this study shows that STAT3 is required for part of the hepatocyte DNA synthetic response after partial hepatectomy. It provides the first in vivo evidence that STAT3 promotes cell cycle progression under physiological growth conditions.
Key findings
- STAT3 deletion was efficient: more than 90% deletion of the STAT3 gene, with virtually no STAT3 mRNA, nuclear protein, or DNA binding activity in Alb+STAT3fl/fl livers after partial hepatectomy.
- Hepatocyte DNA synthesis at 40 h posthepatectomy in Alb+STAT3fl/fl livers was reduced to approximately one-third of control (a 3-fold difference, p < 0.02), with reduced DNA synthesis at other time points; liver mass was nonetheless regained normally after 1 week with no sign of injury.
- In the absence of STAT3, STAT1 was activated instead: a high level of a complex migrating at the STAT1 homodimer position appeared posthepatectomy, confirmed by supershift with anti-STAT1 but not anti-STAT3 antibody, and nuclear STAT1 protein was markedly induced.
- Immediate-early gene activation was abnormal but not identical to IL-6−/− livers: c-fos and junB were significantly reduced at all time points, c-myc peak activation was delayed, IGFBP-1 was reduced 2-fold at 2 h (vs. more than 3-fold in IL-6−/−), and Egr-1 was up-regulated rather than down-regulated. Of 10 STAT3 target genes, only 1 (lymphotoxin receptor) had not previously been identified as an IL-6 target.
- G1 phase cyclins were partially impaired: cyclin D1 was normal early but reduced at the peak of DNA synthesis (40 h) and remained low; cyclin E induction was delayed until 32 h (vs. 16 h in controls) and lower at later time points.
- MAPK activation followed the same kinetics as controls with no consistent or significant difference in phosphorylated Erk1 or Erk2 at any time point, supporting STAT3 and MAPK as independent IL-6 signaling pathways.
Methods
- Liver-specific STAT3 conditional knockout: STAT3fl/fl mice crossed to albumin promoter–driven Cre transgenic mice to generate Alb+STAT3fl/fl mice and Alb−STAT3fl/fl littermate controls; F1 progeny used in all experiments.
- 8–12-week-old mice underwent two-thirds partial hepatectomy (left lateral and median lobes removed) and were sacrificed at various time points; BrdUrd immunohistochemistry quantified labeled hepatocyte nuclei in 12 random 20× fields (~200 cells/field).
- Analyses included Northern blot, Western blot of whole and nuclear liver extracts, electrophoretic mobility shift assay with supershift, cDNA microarray of RNA at 2 h posthepatectomy, and serum index testing.
Limitations
- Stated by the paper: whether STAT1 can substitute for STAT3 in binding HNF-1 requires further analysis; it is unknown whether cyclin E is regulated by IL-6 during liver regeneration because cyclin E expression was not examined in IL-6−/− livers; other IL-6-activated signaling pathways important for normal liver cell function during regrowth await characterization.
- Evident from the text: the microarray comparison was performed at a single time point (2 h posthepatectomy), and the mechanism by which STAT3 normally inhibits STAT1 activation is described as unknown.
Model-written summary. Check it against the paper before relying on it.
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Cites
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Verification
Claims the paper makes
18 of 68 cited sources checked · 8 supported · 1 flagged · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Three did not show IL-6 regulation posthepatectomy but were activated by IL-6 injection in the liver (TDAG51, membrane glycoproteingp130, and Erp72, the endoplasmic reticulum stress protein) (4”
What the sources say
- Disputedcites [4] Li, 2001, Hepatology sourceExperimental — accuracy not yet measured
Table 1 (HEPATOLOGY June 2001 section; page not supplied) lists ERp72, gp130, and TDAG51 with differential expression between IL-6-positive and IL-6-deficient livers two hours after hepatectomy. That is contrary to the claim that these three showed no IL-6 regulation posthepatectomy. The table passage does not clearly establish the claimed injection result for all three. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Disputed
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“STAT3 is rapidly induced during liver regeneration in an interleukin 6 (IL-6)-dependent fashion, and IL-6 is required for normal liver regeneration.”
What the sources say
- Not checked — no full text of the sourcecites [3] Cressman, 1996, Science source
- Supportedcites [4] Li, 2001, Hepatology source
The Results report that Stat3 expression was induced twofold within two hours of partial hepatectomy. The introductory passage under Abstract reports reduced Stat3 induction in IL-6-deficient livers during regeneration, and the Discussion states that IL-6 activates Stat3 after hepatectomy. The paper also states that IL-6 is necessary for normal liver regeneration. Exact pages for these passages are not specified in our copy. (LLM, conf=0.92)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“STAT3 is rapidly induced during liver regeneration in an interleukin 6 (IL-6)-dependent fashion, and IL-6 is required for normal liver regeneration.”
What the sources say
- Not checked — no full text of the sourcecites [3] Cressman, 1996, Science source
- Supportedcites [4] Li, 2001, Hepatology source
The paper states that IL-6 is essential for normal liver regeneration (opening text following the Abstract). The Discussion also says its findings establish IL-6 as a critical component of the normal regenerative response. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“IL-6−/− mice have impaired liver regeneration characterized by liver necrosis and failure, a blunted DNA synthetic response in hepatocytes, and reduced gene activation during G1 phase.”
What the sources say
- Not checked — no full text of the sourcecites [3] Cressman, 1996, Science source
- Partly supportedcites [4] Li, 2001, Hepatology sourceExperimental — accuracy not yet measured
The introductory passage following the Abstract says IL-6-deficient mice have impaired regeneration and liver necrosis after 70% partial hepatectomy. It says they are prone to liver failure, rather than stating that liver failure occurs in all such mice; the claim omits that qualification. (LLM, conf=0.83)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“IL-6−/− mice have impaired liver regeneration characterized by liver necrosis and failure, a blunted DNA synthetic response in hepatocytes, and reduced gene activation during G1 phase.”
What the sources say
- Not checked — no full text of the sourcecites [3] Cressman, 1996, Science source
- Supportedcites [4] Li, 2001, Hepatology source
The Abstract states that genes involved in G0/G1 transition and G1 progression showed reduced induction in IL-6−/− livers during regeneration. It also reports blunted DNA synthesis, liver necrosis and a risk of liver failure after partial hepatectomy, supporting the full citing sentence. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesEvery source the paper cites for this claim was checked and supports it.
In the paper
“However, because IL-6 also activates other signaling pathways including the mitogen-activated protein kinase (MAPK) pathway during liver regeneration (4”
What the sources say
- Supportedcites [4] Li, 2001, Hepatology source
The Discussion states that MAPK activation is delayed in IL-6-deficient livers and that an IL-6 injection induces MAPK phosphorylation in the liver. It explicitly describes IL-6 activation of the MAPK pathway during liver regeneration as a mechanism complementary to Stat3 signaling. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Interleukin-6 (IL-6)1 is known as one of the most important initiators of the regenerative response (3”
What the sources say
- Not checked — no full text of the sourcecites [3] Cressman, 1996, Science source
- Supportedcites [4] Li, 2001, Hepatology source
The Discussion describes IL-6 as an early stimulus during liver regeneration and a critical component of the normal regenerative response. It also links IL-6 to initiation of the regenerative process, supporting the paraphrase in the paper’s liver-regeneration context. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“IL-6−/− mice have impaired liver regeneration characterized by liver necrosis and failure, a blunted DNA synthetic response in hepatocytes, and reduced gene activation during G1 phase.”
What the sources say
- Not checked — no full text of the sourcecites [3] Cressman, 1996, Science source
- Supportedcites [4] Li, 2001, Hepatology source
The passage labeled Abstract states that IL-6-deficient mice have blunted DNA synthesis after 70% partial hepatectomy. This directly supports the attributed claim about a blunted DNA synthetic response during liver regeneration. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“their expression is likely to be directly regulated by STAT3 because their full transactivation requires the STAT binding elements in their promoters (19”
What the sources say
- Partly supportedcites [19] Wagner, 1990, EMBO J. sourceExperimental — accuracy not yet measured
The c-fos promoter experiments (section labeled Introduction; page unavailable) show that a SIF-binding element enhances c-sis/PDGF-induced transcription and that nonbinding mutations abolish induction in the tested constructs. The paper does not address junB or identify SIF as STAT3, and these experiments do not establish that STAT binding elements are required for full transactivation of both genes. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [27] Coffer, 1995, Oncogene
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In IL-6−/− livers, the first peak of MAPK activation is delayed until 12 h compared with 2 h posthepatectomy in IL-6+/+ livers”
What the sources say
- Supportedcites [4] Li, 2001, Hepatology source
The passage accompanying Fig. 6B (Hepatology, June 2001) reports peak p44/p42 MAPK phosphorylation at 2 hours posthepatectomy in IL-6+/+ livers, while activation in IL-6−/− livers was delayed until 12 hours. This matches the cited comparison. (LLM, conf=0.95)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
- Probably not a substantial claim. 14
- It may state two separate claims as one. 21
- The quote only partly states this claim. 1
Every source the paper cites for this claim was checked and supports it.
In the paper
“Specific disruption of STAT3 in T cells revealed that STAT3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis (13”
What the sources say
- Supportedcites [13] Takeda, 1998, J. Immunol. source
The paper’s summary (p. 4652) says the authors specifically disrupted Stat3 in T cells and found impaired IL-6-induced proliferation. The section on IL-6-induced Stat3 activation explains that IL-6 failed to prevent apoptosis in Stat3-deficient T cells, linking the proliferation effect to prevention of apoptosis. (LLM, conf=0.95)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A number of transformed cell lines as well as samples from human cancers are reported to contain constitutively activated STAT3.”
What the sources say
- Not checked — no full text of the sourcecites [20] Yu, 1995, Science source
- Partly supportedcites [21] Cao, 1996, Mol. Cell. Biol. sourceExperimental — accuracy not yet measured
The Abstract (p. 1595) reports constitutively activated Stat3 in all v-Src-transformed cell lines examined. Our copy does not report the same finding in samples from human cancers, so that part of the claim is unsupported. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [22] Turkson, 2000, Oncogene source
- Not checked — no full text of the sourcecites [23] Danial, 1995, Science source
- Not checked — no full text of the sourcecites [24] Nielsen, 1997, Proc. Natl. Acad. Sci. U. S. A. source
- Partly supportedcites [25] Gouilleux-Gruart, 1996, Blood sourceExperimental — accuracy not yet measured
The Results report constitutive DNA-binding by a STAT3-related factor in several patients’ AML samples, supporting the human-cancer-sample part of the claim. The Discussion also cites STAT3-related activity in Src-transformed cells, but it does not establish constitutively activated STAT3 in a number of transformed cell lines; it notes that the factor detected in AML may differ from STAT3. The indexed passages provide no page numbers. (LLM, conf=0.84)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The STAT family consists of seven family members, and in vitro they bind to a similar consensus element on the DNA, TTCnnn(n)GAA (31-33”
What the sources say
- Not checked — no full text of the sourcecites [31] Schindler, 1995, Immunity source
- Not checked — no full text of the sourcecites [32] Schindler, 1995, Annu. Rev. Biochem. source
- Partly supportedcites [33] Seidel, 1995, Proc. Natl. Acad. Sci. U. S. A. sourceExperimental — accuracy not yet measured
The indexed passage on STAT-binding elements (Abstract, p. 3041) supports binding to a broadly similar palindromic DNA element, describing a general TT(N)5AA structure and testing different half-site spacings. It does not state that the STAT family has seven members, or establish the exact TTCnnn(n)GAA consensus given in the claim. (LLM, conf=0.85)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Although they bind to a similar DNA binding site, STATs may interact with co-activator or co-repressor to regulate different sets of their own downstream targets (5”
What the sources say
- Not checked — no full text of the sourcecites [5] Leu, 2001, Mol. Cell. Biol. source
- Not checked — no full text of the sourcecites [38] Look, 1995, J. Biol. Chem. source
- Not checked — no full text of the sourcecites [39] Ohmori, 1997, J. Biol. Chem. source
- Partly supportedcites [40] Schaefer, 1995, Proc. Natl. Acad. Sci. U. S. A. sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reports cooperative activation of a promoter by Stat3β and c-Jun and suggests this could matter for responses involving other STAT proteins. It does not establish that STATs generally bind similar DNA sites or interact with co-repressors to regulate different sets of downstream targets. The similar-site discussion in the introduction concerns Jun and Fos proteins, not STATs. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [41] Ichiba, 1998, J. Biol. Chem. source
- Partly supportedcites [42] Stocklin, 1996, Nature sourceExperimental — accuracy not yet measured
The paper reports that the glucocorticoid receptor acts as a co-activator for Stat5 and proposes that different co-activators could contribute to signaling specificity. It does not establish that STAT family members bind similar DNA sites or interact with co-repressors to regulate distinct sets of downstream targets (section “Functional interactions between Stat5 and the glucocorticoid receptor”; page unavailable in our copy). (LLM, conf=0.85)
- Partly supportedcites [43] Mikita, 1998, J. Immunol. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says STAT proteins can cooperate with other transcription factors and that the interactions probably depend on promoter context; it demonstrates Stat6–C/EBPβ synergy at one promoter. It does not establish that different STATs bind similar DNA sites or that co-repressors help them regulate distinct sets of downstream targets. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [44] Bhattacharya, 1996, Nature source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Regaining liver mass despite deficient DNA synthesis is a general phenomenon in animal models that are defective in liver regeneration, which most likely results from hypertrophy of hepatocytes despite G1/S arrest (3”
What the sources say
- Not checked — no full text of the sourcecites [3] Cressman, 1996, Science source
- Partly supportedcites [18] Greenbaum, 1998, J. Clin. Invest. sourceExperimental — accuracy not yet measured
The Results report markedly reduced DNA synthesis in C/EBPβ-deficient mice without a statistically significant difference in liver-mass reconstitution. The Discussion proposes increased cell size during G1 as an explanation and suggests that the cell-cycle block may occur near G1/S. It does not establish this as a general phenomenon across animal models or demonstrate hepatocyte hypertrophy despite a confirmed G1/S arrest. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [28] Cornell, 1990, Hepatology source
- Not matchedcites [29] Roselli, 1998, Am. J. Physiol.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked — no full text of the sourcecites [30] Yamada, 1997, Proc. Natl. Acad. Sci. U. S. A. source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, there was little STAT3/STAT3 homodimer observed in Alb+STAT3fl/fl livers after surgery, but a high level of complex was detected migrating at the position of the STAT1 homodimer.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By using a mouse cDNA expression array, we successfully identified more than 100 immediate-early genes that are activated at 2 h posthepatectomy, 36% of which also showed IL-6 regulation posthepatectomy.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was a 3-fold difference in the number of hepatocytes undergoing DNA synthesis at 40 h posthepatectomy (p < 0.02) and reduced DNA synthesis at other time points (Fig. 3, A andB)”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“STAT3 was not present in the nucleus in quiescent livers, but the level went up rapidly and peaked around 2 h posthepatectomy in Alb−STAT3fl/fl livers (Fig. 1 B).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Alb+STAT3fl/fl animals regained liver mass normally after 1 week of surgery showing no sign of injury at any time point posthepatectomy (data not shown).”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In control livers, the message was rapidly induced after surgery and remained high until 24 h posthepatectomy, whereas there was only minimum induction of the STAT3 mRNA in Alb+STAT3fl/fl livers (Fig.1 A).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Alb+STAT3fl/fl mice are fertile, they have no developmental abnormalities, and the gross morphology of the liver is also normal.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
In the paper
“A low level of STAT3/STAT1 heterodimer as well as an even lower level of STAT1 homodimer band were also observed as we have reported previously (17”
What the sources say
- Not checked — no full text of the sourcecites [17] Cressman, 1995, Hepatology source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but the putative STAT1/STAT1 homodimer in Alb+STAT3fl/fl livers was disrupted by the α-STAT1 antibody. α-STAT3 antibody had no effect on this complex.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When preincubated with α-STAT3 antibody, the main DNA binding band in Alb− STAT3fl/fllivers was supershifted, and multiple supershift complexes were formed. Anti-STAT1 antibody had no effect on this complex”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“although mass restoration occurred as in IL-6−/− livers (3”
What the sources say
- Not checked — no full text of the sourcecites [3] Cressman, 1996, Science source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cyclin D1 expression was normal at earlier time points during the cell cycle but was reduced at the peak of DNA synthesis (40 h posthepatectomy) and remained low at all later time points in the Alb+ compared with Alb−STAT3fl/fl livers.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Its expression level is 2-fold lower in Alb+ STAT3fl/fl livers than control livers compared with more than 3-fold lower in IL-6−/− livers.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, Egr-1 is expressed at a lower level at 2 h posthepatectomy in IL-6−/− livers but a higher level at all time points in Alb+STAT3fl/fl livers compared with Alb− STAT3fl/fl livers.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The STAT1 protein level was markedly induced in the nucleus of Alb+STAT3fl/fl livers, whereas in control livers there was only a slight increase in the STAT1 level posthepatectomy.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“whereas Alb+STAT3fl/fl animals were viable after hepatectomy with no signs of liver injury.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Because STAT3 deletion leads to embryonic lethality (12”
What the sources say
- Not checked — no full text of the sourcecites [12] Takeda, 1997, Proc. Natl. Acad. Sci. U. S. A. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Liver regeneration after a two-thirds partial hepatectomy provides an excellent in vivo model for studying cell cycle progression and cell proliferation (1”
What the sources say
- Not checked — no full text of the sourcecites [1] Michalopoulos, 1997, Science source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Signal transducer and activator of transcription 3 (STAT3) belongs to the family of STAT transcription factors which mediate the cellular response to a variety of cytokines and growth factors including IL-6 (6-8”
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“From the knock-out mouse models now available, only STAT3 plays an essential role in early embryonic development (12”
What the sources say
- Not checked — no full text of the sourcecites [12] Takeda, 1997, Proc. Natl. Acad. Sci. U. S. A. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“There are two peaks of MAPK activation during regeneration, one at early G1 and the other during mid-late G1 phase.”
What the sources say
- Not checked — no full text of the sourcecites [47] Talarmin, 1999, Mol. Cell. Biol. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The upper band observed in the cyclin E blot (Fig. 7) was most likely the phosphorylated and inactive form of cyclin E.”
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In rat liver, the second peak of activation occurs around 10.5 h, whereas in mouse liver it is around 24 h posthepatectomy, corresponding to a later S phase onset in the mouse liver.”
What the sources say
- Not checked — no full text of the sourcecites [47] Talarmin, 1999, Mol. Cell. Biol. source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“the STAT-binding element in the JunB promoter does not bind or respond to STAT1 (27”
What the sources say
- Not checked — no full text of the sourcecites [27] Coffer, 1995, Oncogene
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The STAT1 knock-out has a specific defect in the interferon-γ response (46”
What the sources say
- Not checked — no full text of the sourcecites [46] Meraz, 1996, Cell source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“the tissue-specific distribution of some STATs may also contribute to their functional specificity (45”
What the sources say
- Not checked — no full text of the sourcecites [45] Zhong, 1994, Proc. Natl. Acad. Sci. U. S. A. source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Furthermore, a constitutively active form of STAT3 causes cellular transformation in immobilized fibroblasts (26”
What the sources say
- Not checked — no full text of the sourcecites [26] Bromberg, 1999, Cell source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The STAT3 conditional deletion in the liver is specific to hepatocytes and does not affect other liver cell types.
“The albumin promoter was chosen to drive the Cre recombinase to obtain liver-specific deletion of the STAT3 gene.”
The paper relies on this without support.
The STAT1 DNA binding activity observed in Alb+STAT3fl/fl livers represents functional STAT1 signaling capable of compensating for STAT3 loss.
“Unlike in control livers, STAT1 was activated in STAT3 conditional-mutant livers posthepatectomy.”
The paper relies on this without support.
The immediate-early gene expression changes at 2 h posthepatectomy are causally responsible for the subsequent hepatocyte DNA synthesis at 40 h.
“This is the first in vivo evidence that STAT3 promotes cell cycle progression and cell proliferation by up-regulating immediate-early growth response genes.”
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?
The cited source doesn’t support the claim as written.
In the citing paper
“Successful LR depends on an intact TNF-NFκB-IL-6-STAT3 pathway.”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [27]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“IL-6, produced following hepatectomy by Kupffer cells and hepatocytes (25), is the central trigger of LR via phosphorylation/activation of STAT3 (27).”
From A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals (2013) · cites this paper as [27]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“By contrast, the effect of liver-specific Stat3 deletion was relatively modest (71, 72)”
From Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2 (2022) · cites this paper as [71]
Citations
Cites
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080
Experimental pathology of the liver
Higgins, G. (1931) · Medical Entomology and Zoology · Cited by 4,057
Darnell, J. E. (1997) · Science · doi:10.1126/science.277.5332.1630 · Cited by 3,979
Michalopoulos, G. K., & DeFrances, M. C. (1997) · Science · doi:10.1126/science.276.5309.60 · Cited by 2,828
Bromberg, J. F., Wrzeszczynska, M. H., Devgan, G., Zhao, Y., Pestell, R. G., Albanese, C., & Darnell, J. E. (1999) · Cell · doi:10.1016/s0092-8674(00)81959-5 · Cited by 2,790
Zhong, Z., Wen, Z., & Darnell, J. E. (1994) · Science · doi:10.1126/science.8140422 · Cited by 2,070
TRANSCRIPTIONAL RESPONSES TO POLYPEPTIDE LIGANDS: The JAK-STAT Pathway
Schindler, C., & Darnell, J. E. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.003201 · Cited by 1,808
Meraz, M. A., White, J. M., Sheehan, K. C. F., Bach, E. A., Rodig, S. J., Dighe, A. S., Kaplan, D. H., Riley, J. K., Greenlund, A. C., Campbell, D., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81288-x · Cited by 1,656
Essential role of Stat6 in IL-4 signalling
Takeda, K., Tanaka, T., Shi, W., Matsumoto, M., Minami, M., Kashiwamura, S.-I., Nakanishi, K., Yoshida, N., Kishimoto, T., & Akira, S. (1996) · Nature · doi:10.1038/380627a0 · Cited by 1,557
Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice
Cressman, D. E., Greenbaum, L. E., DeAngelis, R. A., Ciliberto, G., Furth, E. E., Poli, V., & Taub, R. (1996) · Science · doi:10.1126/science.274.5291.1379 · Cited by 1,538
Self-citation
Flagged first, then by citations
1 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- Higgins, 1931, Arch. Pathol., 12, 186
- Mohn, 1991, Mol. Cell. Biol., 11, 1393
- Coffer, 1995, Oncogene, 10, 985
- Roselli, 1998, Am. J. Physiol., 275, G1472
Cited by
Sorted by citations
Items 201–300 of 306
Jiao, Y., Ye, D. Z., Li, Z., Teta‐Bissett, M., Peng, Y., Taub, R. A., Greenbaum, L. E., & Kaestner, K. H. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00084.2014 · Cited by 18
“In the liver, STAT3 is activated by the IL-6 family cytokines and IL-22, and the IL-6/STAT3 signaling pathway plays a critical role in liver regeneration (6, 15, 19, 22, 25).”
BackgroundInfluentialSelf-citationStärkel, P., Saeger, C. D., Leclercq, I. A., & Horsmans, Y. (2007) · Laboratory Investigation · doi:10.1038/labinvest.3700496 · Cited by 18
“Stat3 is known to play a role in hepatocytes proliferation in rodents.(17,35) Inappropriate constitutive activation of Stat3 does also occur in numerous human cancers.”
Chen, S., Wang, Z., Shichuan, W., et al. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.7561 · Cited by 17
“Cell mitosis then accelerates and stimulates liver cell proliferation (29-36).”
Sugihara, M., Sadamori, H., Nishibori, M., Sato, Y., Tazawa, H., Shinoura, S., Umeda, Y., Yoshida, R., Nobuoka, D., Utsumi, M., et al. (2015) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2015.06.025 · Cited by 17
Liver-specific Ldb1 deletion results in enhanced liver cancer development
Teufel, A., Maass, T., Strand, S., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.05.027 · Cited by 17
“Genotyping was performed as described before [12,17,18].”
The research development of STAT3 in hepatic ischemia-reperfusion injury
Yang, H., Zhang, P., Wang, Q., Cheng, K., & Zhao, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1066222 · Cited by 17
“However, Feng D found that STAT3 had no effect after 6 h of APAP-induced ALI (88, 89) while Nishina T observed that STAT3 was still functional after 24 h; thus the specific relationship between APAP and STAT3 requires further investigation (90).”
BackgroundTyrosine phosphorylation and liver regeneration: A glance at intracellular transducers
Pagano, M. A., Tibaldi, E. V., Gringeri, E., & Brunati, A. M. (2011) · IUBMB Life · doi:10.1002/iub.576 · Cited by 15
“In fact, while ablation of gp130 in conditional knockout mice results in impairment of the early activation of STAT3 with conserved DNA synthesis posthepatectomy (18), the latter process is instead severely hindered early in STAT3 mice (19).”
BackgroundMonocyte chemoattractant protein-1 is not required for liver regeneration after partial hepatectomy
Wyler, S., D’Ingillo, S. L., Lamb, C. L., & Mitchell, K. A. (2016) · Journal of Inflammation · doi:10.1186/s12950-016-0136-1 · Cited by 16
“During the priming phase of regeneration, IL-6 activates STAT3, which upregulates immediate-early gene expression in hepatocytes and promotes responsiveness to growth factors [3, 4].”
BackgroundHepatocyte Turnover in Chronic HCV-Induced Liver Injury and Cirrhosis
Karidis, N. P., Delladetsima, I. K., & Theocharis, S. E. (2015) · Gastroenterology Research and Practice · doi:10.1155/2015/654105 · Cited by 16
Guo, Y., Cui, Q., Ren, S., Hao, D., Morikawa, T., Wang, D., Liu, X., & Pan, Y. (2021) · Journal of Natural Medicines · doi:10.1007/s11418-021-01508-y · Cited by 15
Zou, Z., Cai, Y., Chen, Y., Chen, S., Liu, L., Shen, Z., Zhang, S., Xu, L., & Chen, Y. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3660 · Cited by 15
Alharbi, B., Fadda, L. M., & Ali, H. M. (2018) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22243 · Cited by 16
Huda, K. A. S. M., Guo, L., Haga, S., Murata, H., Ogino, T., Fukai, M., Yagi, T., Iwagaki, H., Tanaka, N., & Ozaki, M. (2006) · Transplant International · doi:10.1111/j.1432-2277.2006.00285.x · Cited by 14
Nakagawa, J., Koyama, Y., Kawakami, A., Ueki, Y., Tsukamoto, H., Horiuchi, T., Nagano, S., Uchino, A., Ota, T., Akahoshi, M., et al. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1387-9 · Cited by 15
“In addition, IL-6 is associated with liver regeneration via a mitogenactivated protein kinase (MAPK) pathway, which promotes hepatocyte proliferation [42, 43].”
BackgroundCentral role of Prominin-1 in lipid rafts during liver regeneration
Bahn, M., Yu, D., Lee, M., Jo, S.-J., Lee, J., Kim, H., Lee, H., Kim, H. L., Kim, A., Hong, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33969-4 · Cited by 15
“The GPIanchor signal sequence from pCAG:GPI-GFP (#32601, Addgene) was added at the C-terminus of PROM1-EX1 (1-99)-FLAG.”
MethodCOOK, D. J., Achanta, S., Hoek, J. B., Ogunnaike, B. A., & Vadigepalli, R. (2018) · BMC Systems Biology · doi:10.1186/s12918-018-0605-7 · Cited by 15
Guo, Y., Zeng, W., Li, R., Zeng, M., Chen, R., Liu, Y., Jiang, R., & Wang, Y. (2022) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2022.07.016 · Cited by 13
“Among regenerative signaling, STAT3 is an acute-phase response factor functioning as a key signal transducer and transcription activator responsible for injury-induced liver regeneration; the IL6/JAK/ STAT3 pathway has a major role in activating the STAT3/ cyclin D1 axis in hepatocytes.(8,24,36) The overall lower expr…”
BackgroundPoli, V., & Alonzi, T. (2003) · Springer eBooks · doi:10.1007/978-94-017-3000-6_31 · Cited by 13
Self-citationOsmotic regulation of STAT3 stability in H4IIE rat hepatoma cells
Lornejad‐Schäfer, M. R., Albrecht, U., Poppek, D., Gehrmann, T., Grune, T., Bode, J. G., Häussinger, D., & Schliess, F. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.09.053 · Cited by 13
“plays a major role in liver regeneration [6], hepatoprotection [7,8], and insulin signaling [9].”
BackgroundLlorens‐Giralt, P., Ruiz‐Romero, M., Nurtdinov, R., Herranz‐Itúrbide, M., Vicent, G. P., Serras, F., Fabregat, I., & Corominas, M. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.100887 · Cited by 11
Fathi, F., Sanei, B., Ganjalıkhani-Hakemi, M., Saidi, R. F., & Rezaei, A. (2021) · Canadian Journal of Gastroenterology and Hepatology · doi:10.1155/2021/5593655 · Cited by 12
“In line with this notion, animal studies have shown that approximately 70% of IL-6 gene knocking out mice failed to have liver regeneration [29].”
Kimura, M., Kurihara, K., Moteki, H., & Ogihara, M. (2021) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/jpps31586 · Cited by 12
“Thus, following GH treatment, JAK1/2 activation was upstream of IGF-I RTK, PI3K, ERK, and mTOR, but not STAT3/5.”
BackgroundLoss of hepatocyte ERBB3 but not EGFR impairs hepatocarcinogenesis
Scheving, L. A., Zhang, X., Stevenson, M. C., et al. (2015) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00089.2015 · Cited by 11
“STAT3 appears to be a key signaling molecule in human HCC (22) as well as liver regeneration (28), and it will be important to determine how hepatocellular ERBB3 diminishes maximal phosphorylation of STAT3.”
BackgroundVaquero, J., Riehle, K. J., Fausto, N., & Campbell, J. S. (2011) · Gastroenterology Research and Practice · doi:10.1155/2011/727403 · Cited by 10
“In mice, this cytokine activation results in an early increase of IL-6 in the circulation, which modulates a variety of genes involved in cell proliferation, survival, and the acute phase response [6, 7].”
Wang, J., Chen, R., Tang, S.-W., Lv, X., Wu, S.-S., Zhang, Y., Xia, Y.-Y., Gao, P.-P., Tu, D.-H., Chen, D.-F., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118862 · Cited by 12
“Li [43] created liver-specific STAT3 deletion mice and reported that these mice exhibited reduced hepatocyte DNA synthesis and lower expression level of G1-phase cyclins, including cyclin D1 and E in the liver.”
BackgroundHe, Z., Lou, K.-H., Zhao, J.-H., Zhang, M., Zhang, L., Ju, L., Yu, H., Zhang, R., & Hu, W. (2020) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2020/2305784 · Cited by 10
“TNF α also activates transcription factors like STAT3 and NF-κ B, which in turn promote the expression of cell cycle regulator genes such as cyclin D [24, 25].”
Athanasopoulos, P., Mastoraki, A. T., Papalois, A. E., Nastos, C., Kondi-Pafiti, A. I., Kostopanagiotou, G. G., Smyrniotis, V. E., & Arkadopoulos, N. F. (2015) · Journal of Investigative Surgery · doi:10.3109/08941939.2015.1060280 · Cited by 10
“tion affects negatively the postoperative liver function [24, 25, 26, 27].”
BackgroundImpact of Cell Cycle Disruption on Impaired Hepatic Regeneration in Aged Livers with Ischemic Insult
Suzuki, A., Sakaguchi, T., Inaba, K., Suzuki, S., & Konno, H. (2010) · Journal of Surgical Research · doi:10.1016/j.jss.2010.10.012 · Cited by 10
Wu, N., Hui, H., Cui, L., & Yang, F. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.09.055 · Cited by 9
Smad3 signaling in the regenerating liver: implications for the regulation of IL-6 expression
Kremer, M., Son, G., Zhang, K., Moore, S. M., Norris, A., Manzini, G., Wheeler, M. D., & Hines, I. N. (2014) · Transplant International · doi:10.1111/tri.12322 · Cited by 9
“In support of this notion are studies which show that loss of Stat3 in hepatocytes reduced their proliferation early during regeneration following partial hepatectomy and to a similar degree following carbon tetrachloride-induced liver damage [6,23,47].”
BackgroundResultDąbrowska, M. M., Panasiuk, A., & Flisiak, R. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.2184 · Cited by 9
A mesoscale model of G1/S phase transition in liver regeneration
Chauhan, A., Legewie, S., Westermark, P. O., Lorenzen, S., & Herzel, H. (2008) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2008.01.020 · Cited by 9
“STAT3 knockout (Li et al., 2002), c-jun deletion (Behrens et al., 2002) and targeted disruption ARTICLE IN PRESS A. Chauhan et al. / Journal of Theoretical Biology 252 (2008) 465–473 469 of the C/EBP-b gene (Greenbaum et al., 1998) can be simulated by decreasing the synthesis rate of IEG.”
BackgroundKurihara, K., Moteki, H., Kimura, M., et al. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173753 · Cited by 8
Miyaaki, H., Ichikawa, T., Nakao, K., Takeshita, S., Shibata, H., Ozawa, E., Akiyama, M., Miuma, S., & Eguchi, K. (2008) · Intervirology · doi:10.1159/000205264 · Cited by 8
“P-STAT3 was seen in only 16 of 59 cases, because almost all of the liver biopsies chosen for this study were at a low level of inflammation. Moreover, the number of P-STAT3 correlated with the platelet count. P-STAT3 is known to play a role in hepatocyte proliferation, and the progression of fibrosis is associated wit…”
BackgroundGenetic and Cellular Contributions to Liver RegenerationPreprint
Liang, R. J., Lin, Y.-H., & Zhu, H. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a040832 · Cited by 8
Wang, T., Wang, M., Liu, W., Zhang, L., Jia, Z., Zhao, J., Wu, Z., Lyu, Y., & Wu, R. (2025) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2025.5483 · Cited by 7
Wang, C.-H., Chen, C.-Y., Wang, K., Kao, A., Chen, Y.-J., Lin, P.-H., Chen, M. J., Wu, T.-Y., Cheng, J., Lee, K., et al. (2023) · Stem Cells Translational Medicine · doi:10.1093/stcltm/szac084 · Cited by 7
A protective role of Stat3 in Fas mediated apoptosis of the liver
Liedtke, C., & Trautwein, C. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.02.020 · Cited by 7
“[7] Li W, Liang X, Kellendonk C, Poli V, Taub R.”
BackgroundHepatic Regenerative Response in Small-Sized Liver Isografts in the Rat
Yao, A. H., Yang, Y., Li, X. C., Pu, L., Zhong, J. W., Liu, X. Z., Yu, Y., Zhang, F., Kong, L., & Wang, X. H. (2009) · Journal of Surgical Research · doi:10.1016/j.jss.2009.02.013 · Cited by 8
Liu, T., Song, J., Zhang, M., et al. (2019) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.22860 · Cited by 6
Liposomal IL-22 ameliorates liver fibrosis through miR-let7a/STAT3 signaling in mice
El-Shorbagy, A. A., Shafaa, M. W., Elbeltagy, R. S., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.111015 · Cited by 6
Backes, A. N., Tannuri, A. C. A., Backes, F. N., et al. (2014) · Pediatric Surgery International · doi:10.1007/s00383-014-3464-3 · Cited by 6
Accelerated liver recovery after acute CCl4 poisoning in rats treated with sodium phthalhydrazide
Danilova, I. G., Шафигуллина, З. А., Гетте, И. Ф., Sencov, V. G., Medvedeva, S. Y., & Abidov, M. T. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2019.106124 · Cited by 6
Vitamin D3 up-regulated protein 1 controls the priming phase of liver regeneration
Kwon, H., Hong, S.-K., Yoon, W., Nam, K., Choi, I., Kim, D.-Y., Kim, H.-C., & Won, Y. (2013) · Journal of Veterinary Science · doi:10.4142/jvs.2013.14.3.257 · Cited by 6
“Ablation of the hepatic STAT-3 gene diminished hepatocyte proliferation after PH or administration of CCl4 [11,20,24].”
BackgroundGenetic factors predicting response to interferon treatment for viral hepatitis C
Stärkel, P. (2008) · Gut · doi:10.1136/gut.2007.137646 · Cited by 6
Hierarchies of Transcriptional Regulation During Liver Regeneration
Kurinna, S. M., & Barton, M. C. (2010) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385233-5.00007-6 · Cited by 5
Hepatotoxicity: A Major Complication with Critical Treatment
Sharma Mukesh, K. (2015) · MOJ Toxicology · doi:10.15406/mojt.2015.01.00016 · Cited by 5
“In the liver, this process promotes liver regeneration [99], the acute-phase response and hepato protection against Fas and toxic damage [100-102,97].”
BackgroundSchattenberg, J. M., & Czaja, M. J. (2009) · Springer eBooks · doi:10.1007/978-3-642-00150-5_10 · Cited by 5
Michalopoulos, G. K. (2010) · Molecular pathology library · doi:10.1007/978-1-4419-7107-4_18 · Cited by 5
Surgical Stress and Liver Response: Injury, Regeneration, and Protection
Ozaki, M., & Haga, S. (2025) · Journal of Surgical Research · doi:10.1016/j.jss.2025.07.039 · Cited by 4
Cao, Z., Qin, L., Liu, K., Yao, C., Li, E., Hao, X., Wang, Μ., Jiang, B., Zou, Y., Hu, H., et al. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003357 · Cited by 5
“Given the critical role of STAT3 in driving hepatocyte proliferation during liver regeneration [34–36 During liver regeneration, IL-6 secreted by macrophages and hepatocytes binds to the receptors on hepatocytes to activate JAK family proteins, leading to phosphorylation of STAT3 [28,37–39].”
Rudnick, D. A. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-398523-1.00025-2 · Cited by 4
Tang, H., Fang, H., Guo, W., et al. (2021) · Molecular Biology Reports · doi:10.1007/s11033-020-06090-2 · Cited by 4
Hossen, M. J., Matin, M. A., Sikder, M. H., Ahmed, M. S., & Rahman, M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-822368-0.00016-5 · Cited by 4
STAT3 Mediates Protection From Liver Inflammation After Partial Hepatectomy
Xu, Y., Feng, D., Wang, Y., Luo, Q., & Xu, L. (2009) · Cellular Physiology and Biochemistry · doi:10.1159/000218184 · Cited by 4
de Jonge, J., & Olthoff, K. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-34062-5.00006-6 · Cited by 4
LIFR recruits HGF-producing neutrophils to promote liver injury repair and regenerationPreprint
Deng, Y., Zhao, Z., Sheldon, M., Zhao, Y., Teng, H., Martinez, C., Zhang, J., Lin, C., Sun, Y., Fan, Y., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.18.533289 · Cited by 4
Wang, B., Li, D., Li, J., An, W., Li, Z., Shao, Q., & Qin, L. (2022) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2022.105586 · Cited by 3
Simulated model of RAPID concept: highlighting innate inflammation and liver regeneration
Shi, J., Yan, X., Zhang, S. J., et al. (2020) · BJS Open · doi:10.1002/bjs5.50322 · Cited by 3
Promotion of NR1I3-mediated liver growth is accompanied by STAT3 activation
Mazin, M. E., Yarushkin, A. A., Pustylnyak, Y. A., Prokopyeva, E. A., & Pustylnyak, V. O. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07340-1 · Cited by 3
“Additionally, inhibition of hepatic STAT3 reduces the mitogenic response after partial hepatectomy [9, 10].”
BackgroundPlatelet and Liver Regeneration
Ohkohchi, N., Murata, S., & Takahashi, K. (2012) · InTech eBooks · doi:10.5772/25422 · Cited by 3
“, 2010), signal transducer and activator of transcription 3 (STAT3) (Cressman et al., 1995; Li et al., 2002; Moh et al., 2007), and phosphatidylinositol-3-kinase (PI3K)/Akt (Jackson et al.”
BackgroundHepatitis C virus-host interactions: Etiopathogenesis and therapeutic strategies
Hassan, M. (2012) · World Journal of Experimental Medicine · doi:10.5493/wjem.v2.i2.7 · Cited by 3
IL-1R1 deficiency impairs liver regeneration after 2/3 partial hepatectomy in aged mice
Li, D., Wang, Z., Zhang, C., & Xu, C. (2021) · TURKISH JOURNAL OF BIOLOGY · doi:10.3906/biy-2010-51 · Cited by 3
“STAT3 was necessary for the activation of cyclin D1 (Li et al., 2002), perhaps besides NF-κB the decreased phosphorylation of STAT3 also caused the delayed expression of cyclin D1, which delayed the proliferation of liver cells in IL-1R1 KO mice, as demonstrated by PCNA.”
MethodNature and Function of Hepatic Tumor Necrosis Factor-α Signaling
Schattenberg, J. M., & Czaja, M. J. (2005) · Springer eBooks · doi:10.1007/3-540-27194-5_10 · Cited by 3
“Subsequent investigations in Il-6 null mice suggested that this cytokine is critical for liver regeneration and survival after partial hepatectomy [24], in part through the activation of STAT3 [66].”
BackgroundImmune cells in liver regeneration: Current evidence and potential clinical targets
Moore, H. F., Usmani, S., Froghi, S., Rashidi, H., Quaglia, A., Fuller, B. J., & Davidson, B. R. (2025) · International Reviews of Immunology · doi:10.1080/08830185.2025.2531820 · Cited by 4
“Indeed, IL-22 is known to prevent hepatocyte damage during acute liver inflammation via STAT3 signaling, which induces expression of antiapoptotic and pro-proliferative proteins [24,77,157,158].”
SerpinB3 as hepatic marker of post-resective shear stress
Gringeri, E., Villano, G., Brocco, S., Polacco, M., Calabrese, F., Sacerdoti, D., Cillo, U., & Pontisso, P. (2023) · Updates in Surgery · doi:10.1007/s13304-023-01531-6 · Cited by 3
Zhang, F., Shu, R., Wu, X., Zhao, X., Feng, D., Wang, L., Lu, S., Liu, Q., Xiang, Y., Fei, J., et al. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.04.009 · Cited by 2
“Both of them are activated to promote the process of iver regeneration (Chen et al., 2004; Coqueret, 2002; Li et al., 2002; alarmin et al., 1999).”
BackgroundIdentification of de novo STAT3 target gene in liver regeneration
Zhang, H., Haga, S., Fukai, M., Oikawa, Y., Inoue, H., Ogawa, W., Kano, A., Maruyama, A., Fu, X.-Y., Todo, S., et al. (2007) · Hepatology Research · doi:10.1111/j.1872-034x.2007.00278.x · Cited by 2
Nathan, A. A., & Balakrishnan, A. S. (2017) · Journal of Bacteriology & Parasitology · doi:10.4172/2155-9597.1000322 · Cited by 2
“Existing data support the involvement of pro-inflammatory cytokines namely Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were significantly elevated in LF [2], which plays a key role in the initiation of irreversible swelling, fibrosis [11,12] and regenerative processes of hepatic structure and function [13,14].”
BackgroundHepatotoxicity: A Major Complication with Critical Treatment
Sharma Mukesh, K. (2015) · MOJ Toxicology · doi:10.15406/mojt.2015.02.00016 · Cited by 2
Trautwein, C. (2006) · Elsevier eBooks · doi:10.1016/b978-1-4160-3258-8.50007-3 · Cited by 2
Park, J., Kil, Y., Yi, H. J., Seo, E. K., & Woo, H. A. (2025) · Antioxidants · doi:10.3390/antiox14101210 · Cited by 1
“STAT3 plays a critical role in liver regeneration, as demonstrated in previous studies [46,47].”
Hepatocytes and Progenitor - Stem Cells in Regeneration and Therapy
Amicone, L., Citarella, F., Tripodi, M., & Cicchini, C. (2012) · InTech eBooks · doi:10.5772/45602 · Cited by 1
Ye, S., Dong, J., & Han, B.-L. (2009) · Archives of Medical Research · doi:10.1016/j.arcmed.2009.02.003 · Cited by 1
“The routine biotine streptavidin immunohistochemical staining was performed on slides as described (18), which consisted of sequential incubations in horse serum blocking solution, monoclonal anti-PCNA (clone PC10; Dako, Carpinteria, CA), biotinylated horse anti-mouse immunoglobulin G and streptavidin conjugated to a…”
Methodde Jonge, J., & Olthoff, K. M. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-1454-8.00005-9 · Cited by 1
Nevzorova, Y. A., & Trautwein, C. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-0881-3.00002-4 · Cited by 1
Stem cell signaling molecules and pathways in liver regeneration
Chawla, S., & Das, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18800-8.00014-9 · Cited by 1
The role of microRNAs in the different phases of liver regeneration
Kern, A. E., Ortmayr, G., Assinger, A., & Starlinger, P. P. (2023) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2023.2267422 · Cited by 2
“This ultimately results in the activation of Janus kinase 1 (JAK1) and further Mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3-kinase (PI3K) and signal transducer and activator of transcription 3 (STAT3) pathways [65,66].”
BackgroundBioengineering Liver Transplantation
van der Laan, L. J. W., Spee, B., & Verstegen, M. M. A. (2019) · MDPI eBooks · doi:10.3390/books978-3-03921-745-8 · Cited by 1
Papel de la caveolina en proliferación y en regeneración hepática
Moñibas, R. M., & Gomar, L. B. (2011) · Tesis Doctorals en Xarxa (Consorci de Serveis Universitaris de Catalunya) · doi:10.13140/2.1.3048.1443 · Cited by 1
Immune cell communication in liver disease and liver regeneration
Boghal, R. H., Stephenson, B. F., & Afford, S. C. (2015) · Wiley eBooks · doi:10.1002/9781118663387.ch8 · Cited by 1
Taub, R. A. (2005) · Springer eBooks · doi:10.1007/3-540-27194-5_7 · Cited by 1
Self-citationDent, P., Curiel, D. T., & Fisher, P. B. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-221-2_15
Bösch, R. V. (2010) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.10.2010.tde-03082010-120238
Immune Cell Communication and Signaling Systems in Liver Disease
Bhogal, R. H., & Afford, S. C. (2009) · Springer eBooks · doi:10.1007/978-3-642-00150-5_8
Russo, F. P., Burra, P., & Parola, M. (2013) · Stem cell biology and regenerative medicine · doi:10.1007/978-1-4614-9569-7_13
Tissue-Specific Function of STAT3
Takeda, K., & Akira, S. (2003) · Springer eBooks · doi:10.1007/978-94-017-3000-6_32
Gomez, D. (2012) · Gastroenterology Research · doi:10.4021/gr449w
“This leads to a cascade of events that allows progression of the cell cycle, and subsequent cellular mitosis [14].”
BackgroundResponse and Resistance to Ionizing Radiation
Dent, P., Yacoub, A., Hagan, M. P., et al. (2007) · Humana Press eBooks · doi:10.1007/978-1-59745-035-5_27
ROLE OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 DURING LIVER REGENERATION
Wyler, S. (2015) · Scholar Works (Boise State University)
Involvement of transcription factors in acute pancreatitis
Shigekawa, M., & Takehara, T. (2014) · Suizo · doi:10.2958/suizo.29.38
Liu, T., Zhang, M., Song, J., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24053
“However, STAT3 promotes cell cycle progression and cell proliferation of hepatocytes in response to liver regeneration [47, 48].”
BackgroundTranscriptional programs during mammalian cell prolifération
Rib, L. (2016) · IRIS
Izquierdo, A. L. (2012) · Buleria (Universidad de León) · doi:10.18002/10612/2243
Acute liver failure — mechanisms of liver cell destruction
Trautwein, C., Liedtke, C., Streetz, K. L., Luedde, T., & Klein, C. (2007) · Springer eBooks · doi:10.1007/1-4020-4144-6_25
Tordjmann, T. (2009) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1168253.630406
Shriki, A., Lanton, T., Sonnenblick, A., Levkovitch‐Siany, O., Eidelshtein, D., Abramovitch, R., Rosenberg, N., Pappo, O., Elgavish, S., Nevo, Y., et al. (2023) · doi:10.1158/0008-5472.c.6512938.v1
Li, W., Ye, S., Sun, R., Liu, Y., Tang, Z., Kim, Y., Karras, J. G., & Zhang, H. (2023) · doi:10.1158/1078-0432.c.6518362.v1
Self-citationWang, T., Wang, M., Liu, W., Zhang, L., Zhang, J., Bi, J., Zhao, J., Wu, Z., Lv, Y., & Wu, R. (2024) · Research Square · doi:10.21203/rs.3.rs-3840462/v1
Metadata
- Authors
- Li, W., Liang, X., Kellendonk, C., Poli, V., & Taub, R.
- Affiliations
- University of Pennsylvania (US)
- Columbia University (US)
- University of Dundee (GB)
- Corresponding author
- Taub, Rebecca
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 277
- Issue
- 32
- Pages
- 28411-28417
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2052467994
- Cited by
- 307
- References
- 49
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 11 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 15 · 2017: 10 · 2016: 9 · 2015: 17 · 2014: 13 · 2013: 11 · 2012: 23
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- National Institutes of Health (5r01dk058315-05, 5p30dk050306-29)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 58315, P30DK50306)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- STAT3, liver regeneration, hepatocyte proliferation, interleukin-6, STAT1, partial hepatectomy, G1/S transition, MAPK signaling, hepatocyte DNA synthesis
- MeSH terms
- Animals, Bromodeoxyuridine, Cell Division, DNA, DNA-Binding Proteins, Immunohistochemistry, Liver, Regeneration, Time Factors, Blotting, Northern, Blotting, Western, Signal Transduction, Trans-Activators, DNA, Complementary, Cyclin E, Cyclin D1, Oligonucleotide Array Sequence Analysis, MAP Kinase Signaling System, Hepatocytes, STAT1 Transcription Factor, STAT3 Transcription Factor, Mice
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