The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index; 9 of the 40 sources its claims cite were checked for support.
Expression of suppressors of cytokine signaling during liver regeneration
Open accessAbstract
The cytokines TNF and IL-6 play a critical role early in liver regeneration following partial hepatectomy (PH). Since IL-6 activates signal transducers and activators of transcription (STATs), we examined whether the suppressors of cytokine signaling (SOCS) may be involved in terminating IL-6 signaling. We show here that SOCS-3 mRNA is induced 40-fold 2 hours after surgery. SOCS-2 and CIS mRNA are only weakly induced, and SOCS-1 is not detectable. SOCS-3 induction after PH is transient and correlates with a decrease in STAT-3 DNA binding and a loss of tyrosine 705 phosphorylation. This response is markedly reduced in IL-6 knockout (KO) mice. TNF injection induces SOCS-3 mRNA in wild-type mice (albeit weakly compared with the increase observed after PH) but not in TNF receptor 1 or IL-6 KO mice. In contrast, IL-6 injection induces SOCS-3 in these animals, demonstrating a requirement for IL-6 in SOCS-3 induction. IL-6 injection into wild-type mice also induces SOCS-1, -2, and CIS mRNA, in addition to SOCS-3. Together, these results suggest that SOCS-3 may be a key component in downregulating STAT-3 signaling after PH and that SOCS-3 mRNA levels in the regenerating liver are regulated by IL-6.
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Written from the paper’s full text.
TL;DR
After partial hepatectomy, SOCS-3 mRNA and protein are induced transiently in mouse liver, correlating with STAT-3 activation and inactivation. IL-6 is a major regulator of this SOCS-3 induction, while TNF alone induces a weaker, different SOCS profile.
Key findings
- PH induces SOCS-3 mRNA 40- to 50-fold at 2 hours, sustained for 4 hours, declining by 8 hours and returning to baseline by 24 hours; SOCS-3 protein is detected from 2 hours through 8–10 hours. SOCS-2 and CIS are only weakly induced (four- to tenfold, sometimes undetectable), and SOCS-1 is not induced.
- STAT-3 tyrosine 705 phosphorylation and DNA binding are transient after PH: phosphorylation is first detected at 2 hours and decreases to background by 8 hours; robust DNA binding appears at 2 hours and disappears between 3 and 6 hours. Sham-operated mice show weaker STAT-3 DNA binding.
- In IL-6 KO mice after PH, SOCS-3 mRNA induction is severely reduced and SOCS-3 protein is not detected; STAT-3 tyrosine phosphorylation is weaker and DNA binding is impaired. Densitometry showed approximately a threefold induction of SOCS-3 at 2 hours in WT versus IL-6 KO liver.
- TNF injection induces SOCS-3 in WT mice (<15-fold) but not in TNF-R1 or IL-6 KO mice; IL-6 injection induces SOCS-3 40- to 60-fold in all three strains and also induces SOCS-1, -2, and CIS, unlike PH.
Methods
- Male C57BL/6 WT, IL-6 KO, and TNF-R1 KO mice underwent two-thirds partial hepatectomy or sham laparotomy; some mice received intraperitoneal mTNF (25 µg/kg) or hIL-6 (1 mg/kg), with saline controls.
- Liver tissue was analyzed by Northern blot for SOCS-1, -2, -3, and CIS mRNA normalized to cyclophilin, by EMSA for STAT DNA binding and supershift, and by immunoprecipitation/immunoblot for STAT-3 phosphorylation and SOCS-3 protein.
- Data were analyzed by one-way ANOVA followed by Newman-Keuls test; cell culture controls included IL-6-stimulated AML12, HepG2, and RAW 264.7 cells.
Limitations
- The paper states that more precise analysis of SOCS-3’s role awaits SOCS-3-transgenic or knockout mice, and that such systems require conditional expression because constitutive expression or ablation causes embryonic death.
- The paper reports that Western blot detection of CIS, SOCS-1, and SOCS-2 proteins was unsuccessful because commercially available antibodies could not detect these proteins in liver lysates.
- Evident from the text: the main findings are correlative timing and loss-of-function cytokine/receptor models rather than direct SOCS-3 perturbation; the authors also note that a single IL-6 injection does not faithfully reproduce PH signaling and that other cytokines may contribute to SOCS-3 induction after PH.
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Claims the paper makes
9 of 40 cited sources checked · 7 supported · 0 flagged · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“These studies and others suggest that IL-6 participates in hepatocyte proliferation in vivo not only in PH but in injury-induced models of liver proliferation (12).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
- Supportedcites [12] Streetz, 2000, Gut source
The ‘Importance of IL-6 during liver regeneration’ section (page not provided) describes IL-6-dependent hepatocyte proliferation after partial hepatectomy and reports that IL-6 promotes hepatocyte proliferation after liver ischaemia and reperfusion. It also discusses regeneration following Con-A-induced liver injury, supporting the claim's extension to injury-induced models. (LLM, conf=0.92)
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
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
“No STAT-1 homodimer activity was seen in these experiments.”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“Sham-operated mice have a detectable, but much weaker STAT-3 DNA-binding activity (Figure 1b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“Use of STAT-1 and STAT-5 oligonucleotide probes demonstrates that STAT-3 is the major STAT family member activated after PH (Figure 1c).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Importantly, tyrosine 705 phosphorylation of STAT-3 correlates with its ability to bind DNA (Figure 1b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“After PH, SOCS-3 mRNA is much more sustained because mRNA is detected between 2 and 8 hours after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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, after PH, SOCS-3 induction is approximately sixfold greater than CIS.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“While SOCS-1 mRNA was not induced by PH, CIS and SOCS-2 mRNA was detectable, albeit much weaker than SOCS-3 (data not shown).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“A weak induction of SOC-3 is detectable in sham-operated mice (Figure 2).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“Figure 5 shows that TNF injection into WT mice induces SOCS-3 in a time-dependent manner compared with control and saline injection.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Only STAT-3 homodimers are seen after PH (Figure 2c and ref. 16).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Not checked — no full text of the sourcecites [16] Cressman, 1995, Hepatology source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Compared with SOCS-3, which is induced 40-to 60-fold after PH, CIS and SOCS-2 were only weakly induced.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Sham-operated mice also have a detectable, but much weaker STAT-3 tyrosine 705 phosphorylation and DNAbinding capacity (Figure 4a and Figure 1b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Defective induction of STAT-3 in IL-6 KO mice after PH.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“SOCS-3 has not been shown to have catalytic phosphatase activity, yet by 8 hours after PH, STAT-3 is no longer tyrosine phosphorylated (Figure 1a).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Figure 6 shows that IL-6 injection induces SOCS-3 mRNA in all three genetic strains, indicating that IL-6 can bypass the defects in TNF-R1-and IL-6 KO mice.”
§ Expression of suppressors of cytokine signaling during liver regeneration > IL-6 injection induces SOCS-3 mRNA in TNF-R1-and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“It is important to note that PH induces SOCS-3 to much higher levels (>40-fold) than TNF injection (<15-fold) (compare Figure 5b to Figure 2b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 IL-6 KO mice, STAT-3 tyrosine phosphorylation was detectable by 2 hours after surgery, although it was weaker than the levels seen in WT animals (Figure 4a, top).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Defective induction of STAT-3 in IL-6 KO mice after PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In addition to SOCS-3, injection of IL-6 induces CIS, SOCS-1, and SOCS-2 mRNA (Figure 6) in the liver, an observation reported by other laboratories (20).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Not checked — no full text of the sourcecites [20] Starr, 1997, Nature source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“Detection of SOCS-3 protein is consistent with the induction of SOCS-3 mRNA (Figure 2a).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Although SOCS-3 message levels were induced compared with either control or sham-operated mice, SOCS-3 mRNA induction in the IL-6 KO liver was severely reduced after PH compared with WT tissue (Figure 3, a and b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Blunted induction of SOCS-3 in IL-6 KO mice after PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“While SOCS-1 mRNA was not induced by PH, CIS and SOCS-2 mRNA was detectable, albeit much weaker than SOCS-3 (data not shown).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 studies presented here show that SOCS-3 transcripts and protein are induced during the priming phase of liver regeneration and that this induction is greatly diminished in IL-6 KO mice.”
§ Expression of suppressors of cytokine signaling during liver regeneration > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 magnitude of SOCS-3 induction after IL-6 injection is now comparable with that seen after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > IL-6 injection induces SOCS-3 mRNA in TNF-R1-and IL-6 KO mice.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“One notable exception is the human hepatoma cell line, HepG2 (Figure 1c), where SIF A, B (STAT-3:STAT-1), and C (STAT-1:STAT-1) DNA complexes are all detected after IL-6 treatment (30).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Not checked — no full text of the sourcecites [30] Bode, 1999, FEBS Lett source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe 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
“The SOCS-3 induction is not completely abolished in IL-6 KO mice after PH, perhaps uncovering the actions of other cytokines.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 studies presented here show that SOCS-3 transcripts and protein are induced during the priming phase of liver regeneration and that this induction is greatly diminished in IL-6 KO mice.”
§ Expression of suppressors of cytokine signaling during liver regeneration > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Moreover, SOCS-1 and -2 mRNA levels are detectable after TNF injection.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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, CIS, SOCS-1, and SOCS-2 are not strongly induced after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“SOCS-3 mRNA is rapidly induced in the mouse liver after PH compared with sham-operated animals (Figure 2, a and b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Densitometry analysis showed that at 2 hours after PH there was approximately a threefold induction of SOC-3 in livers of WT mice compared with IL-6 KO mice (data not shown).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Blunted induction of SOCS-3 in IL-6 KO mice after PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Additionally, we find that the magnitude of induction and spectrum of SOCS molecules that are induced is markedly different after TNF injection when compared with that seen after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Similar to Cressman et al. ( 9), our results show that STAT-3 DNA-binding activity is greatly impaired after PH in IL-6 KO mice liver.”
§ Expression of suppressors of cytokine signaling during liver regeneration > Defective induction of STAT-3 in IL-6 KO mice after PH.
What the sources say
- Not checked — no full text of the sourcecites [9] Cressman, 1996, Science source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“After TNF injection, we see that SOCS-3 induction is about twofold greater than CIS induction.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“However, the ability of STAT-3 to bind DNA was impaired (Figure 4b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Defective induction of STAT-3 in IL-6 KO mice after PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“IL-6 injection induces SOCS-3 message levels 40-to 60-fold (Figure 6, a and b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > IL-6 injection induces SOCS-3 mRNA in TNF-R1-and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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 TNF-R1 KO or IL-6 KO mice were injected with TNF, we found that TNF did not induce SOCS-3 in the liver of either mouse strain (Figure 5b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“None of the other SOCS messages were detectable (data not shown).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Blunted induction of SOCS-3 in IL-6 KO mice after PH.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe 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
“While SOCS-3 is induced after PH and the timing of its expression correlates very well with the inactivation of STAT-3 DNA binding, more precise analysis of the role of SOCS-3 awaits the establishment of SOCS-3-transgenic or KO mice.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Moreover, in mice lacking either TNF receptor 1 (p55/TNF-R1) or IL-6, hepatocyte proliferation and liver mass restoration are significantly impaired after PH (8,9).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Supershift analysis con-firms that the STAT-3 DNA-binding activity being measured is due to a STAT-3 homodimer, not a STAT-1:STAT-3 heterodimer (Figure 1d).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Two known regulators of the priming phase of liver regeneration are the cytokines TNF and IL-6 (7)(8)(9).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
- Not matchedcites (7)(8)(9)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Not matched
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
“Thus two mechanisms, SOCS-3 and a tyrosine phosphatase, may coexist to ensure complete inhibition of cytokine signals mediated by STATs.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: STAT-3 induces SOCS-3 mRNA, leading to an increase in SOCS-3 protein levels, which downregulate IL-6-stimulated STAT-3.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Western blot analysis detection of CIS, SOCS-1, and SOCS-2 proteins was unsuccessful as the commercially available Ab's (Santa Cruz Biotechnologies Inc. and Zymed Inc., Camarillo, California, USA) were unable to detect these proteins in liver lysates (data not shown).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Immunoblot analysis.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA 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
“SOCS-3 appears to be the major isoform regulating cytokine signaling during liver regeneration.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: STAT-3 induces SOCS-3 mRNA, leading to an increase in SOCS-3 protein levels, which downregulate IL-6-stimulated STAT-3.
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
“Inhibition of STAT-3 signaling may ensure the termination of the priming phase of liver regeneration.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: STAT-3 induces SOCS-3 mRNA, leading to an increase in SOCS-3 protein levels, which downregulate IL-6-stimulated STAT-3.
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
“In contrast, induction of CIS after TNF injection seems to require only TNF-R1 and not IL-6.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Since SOCS-3 induction is severely blunted in IL-6 KO liver after PH, the induction of SOCS-3 after PH is, for the most part, dependent on IL-6.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Moreover, the lack of induction of the other SOCS isoforms after PH suggests that a single injection of IL-6 does not faithfully reproduce the signaling parameters of PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“These data suggest that TNF is not the sole mediator of SOCS-3 induction after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Priming and progression of hepatocyte proliferation after PH requires the actions of TNF and IL-6 and growth factors such as TGF-α and HGF (1,3,5,27).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Discussion
What the sources say
- Not checked — no full text of the sourcecites [1] Fausto, 2000, J Hepatol source
- Not checked — no full text of the sourcecites [3] Michalopoulos, 1997, Science source
- Not checked — no full text of the sourcecites [5] Taub, 1999, Semin Liver Dis source
- Not checked — no full text of the sourcecites [27] Brenner, 1998, J Gastroenterol Hepatol source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Besides IL-6, there must be other factors, cytokines, or growth factors, that directly or indirectly influence SOCS-3 induction after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“These results suggest that IL-6 is a major regulator of SOCS-3 induction after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > Blunted induction of SOCS-3 in IL-6 KO mice after PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“Thus in liver regeneration, SOCS-3 participates in a negative-feedback loop turning off IL-6-mediated STAT-3 activation.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: STAT-3 induces SOCS-3 mRNA, leading to an increase in SOCS-3 protein levels, which downregulate IL-6-stimulated STAT-3.
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
“Oncostatin M (OSM), leukemia inhibitory factor (LIF), and cardiotrophin-1 (CT-1), members of the IL-6 cytokine family that can induce STAT-3 DNA binding, could be the cytokines that cooperate with IL-6 during regeneration.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA 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
“SOCS-3 appears to play an important role in inhibiting the IL-6-signaling pathway.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 13
- It may state two separate claims as one. 33
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In the liver, IL-6 activates multiple signaling pathways that culminate in the induction of genes involved in growth, hepatocyte-specific metabolic functions, and the acute-phase response (13).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
- Partly supportedcites [13] Heinrich, 1990, Biochem J sourceExperimental — accuracy not yet measured
The section on IL-6-responsive elements in acute-phase protein genes reports IL-6-induced gene transcription, and the Actions section describes increased acute-phase protein synthesis in human hepatocytes. But the Signal transduction section says the underlying mechanisms were still unknown; the cited passages do not establish multiple signaling pathways or induction of genes for hepatocyte growth and specific metabolic functions. Page numbers are unavailable in our copy. (LLM, conf=0.87)
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.
- Partly 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
“When IL-6 binds to its receptor complex composed of a specific receptor subunit, the IL-6 receptor (IL-6R), and a gp130 homo dimer, a cascade of signaling events is initiated, most notably the Jak/STAT pathway (14,15).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
- Supportedcites [14] Heinrich, 1998, Biochem J source
The IL-6-type cytokine receptor complexes section says IL-6 induces gp130 homodimerization, and the IL-6-type-cytokine-receptor interactions section describes IL-6 binding to IL-6R. The Signalling of IL-6-type cytokines section identifies Jak kinases and STAT factors as major mediators of the resulting signal transduction. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [15] Imada, 2000, Mol Immunol 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.
- 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
“The levels of these cytokines increase after PH, with the peak of TNF circulating levels preceding the peak levels of IL-6 (8,10,11).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
- Not checked — no full text of the sourcecites [8] Yamada, 1997, Proc Natl Acad Sci USA source
- Supportedcites [10] Trautwein, 1996, Gastroenterology source
The “Cytokine Levels After Hepatectomy and Sham Surgery” section reports that liver-vein IL-6 rose after hepatectomy and peaked at 6 hours. It also reports that TNF-α peaked at 2 hours posthepatectomy (p. 1855), preceding the IL-6 peak. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [11] Akerman, 1992, Am J Physiol source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“These cytokines have been implicated in liver functions such as development, hepatocyte differentiation, or inflammation (31)(32)(33), but have yet to be examined in liver regeneration.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Not checked — no full text of the sourcecites [31] Miyajima, 2000, Cytokine Growth Factor Rev source
- Partly supportedcites [32] Peters, 1995, FEBS Lett sourceExperimental — accuracy not yet measured
The Introduction and Results and discussion link CT-1, LIF, and OSM to hepatocyte acute-phase responses associated with inflammation. The paper does not address liver development or hepatocyte differentiation, and although it does not study liver regeneration, it does not establish that these cytokines had yet to be examined in that setting. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [33] Omori, 1996, Lab Invest
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“In the first mechanism, nascent SOCS-3 blocks the activation of STAT-3 by binding to the receptor complex via gp130 at tyrosine 759 (34,35) and/or by binding and inhibiting Jak2 activity (36).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Supportedcites [34] Schmitz, 2000, J Biol Chem source
The citation is attached to the gp130 Tyr-759 mechanism, while a separate citation follows the Jak2 mechanism. In the sections on SOCS3 binding and STAT3 activation, the paper reports that SOCS3 binds phosphorylated Tyr-759 of gp130 and that mutation of this site impairs SOCS3-mediated inhibition of STAT3 activation. (LLM, conf=0.92)
- Supportedcites [35] Nicholson, 2000, Proc Natl Acad Sci USA source
The Discussion identifies human gp130 Y759 as equivalent to mouse Y757, and the Results show that SOCS-3 binds at mouse gp130 pY757 and that mutation of this site impairs its inhibition of gp130 signaling. The Discussion also reports suppression of STAT3 phosphorylation. The separate claim about binding and inhibiting Jak2 is attached to citation 36, not to this source. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [36] Krebs, 2000, J Cell Sci source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- 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
“Possible tyrosine phosphatases include an unidentified nuclear tyrosine phosphatase activity that has been reported to inactivate IFN-γ-stimulated STAT-1 (37) and the SH2-containing phosphatases, SHP-1 and SHP-2, which regulate cytokine signals in other tissues (38).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Supportedcites [37] Haspel, 1999, Proc Natl Acad Sci USA source
The Abstract reports evidence that a nuclear tyrosine phosphatase plays a major role in inactivating Stat1 after IFN-γ treatment. The Discussion identifies nuclear dephosphorylation as the study’s major conclusion. The SHP-1 and SHP-2 statement carries a separate citation and is not attributed to this paper. (LLM, conf=0.93)
- Not checked — no full text of the sourcecites [38] Feng, 1999, Exp Cell Res 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. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These expression systems require conditional expression of SOCS-3 within the parenchymal cells of the liver since constitutive expression or ablation results in embryonic death (40).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Supportedcites [40] Marine, 1999, Cell source
The Abstract (p. 1) states that transgene-mediated SOCS3 expression blocks fetal erythropoiesis and results in embryonic lethality, while SOCS3 deletion also results in embryonic lethality. The Results describe the effects of constitutive expression (p. 5) and confirm lethality after deletion (p. 6). (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
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
“As has been demonstrated previously (8, 9, 16), robust STAT-3 DNA-binding activity is detected by 2 hours and rapidly disappears between 3 to 6 hours.”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
What the sources say
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
“STAT-3 tyrosine 705 phosphorylation is first detected by 2 hours after surgery and decreases to background levels by 8 hours (Figure 1a, top).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
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
“Phosphorylation of serine 727 of STAT-3 can be weakly detected (Figure 1a, middle), but the signal is variable.”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
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
“Increased SOCS-3 protein levels were first detected by 2 hours with sustained expression until 8 and 10 hours (Figure 2c, top).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ 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
“Both STAT-3 activity and SOCS-3 protein are no longer detectable by 8 hours after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
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
“The low level of tyrosine 705 phosphorylation of STAT-3 in the KO mice after PH correlates with weak STAT-3 DNA binding (Figure 4b) and weak induction of SOCS-3 (Figure 3a).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Defective induction of STAT-3 in IL-6 KO mice after PH.
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
“TNF injection also transiently induces CIS mRNA (Figure 5b) and SOCS-2 and SOCS-1 mRNAs (data no shown).”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Strength:plain· not yet calibratedCausal:direct· 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
“However, IL-6 injection also induces SOCS-1, -2, and CIS mRNA expression, a pattern not seen after PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > IL-6 injection induces SOCS-3 mRNA in TNF-R1-and IL-6 KO mice.
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
“SOCS-3 message is first detected at 1 hour and disappears rapidly (Figure 5a).”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
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
“In contrast to SOCS-3, CIS is induced in the liver of IL-6 KO mice but not in TNF-R1 KO mice.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
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
“SOCS-3 mRNA is induced by 1 hour and rapidly declines by 2 hours after IL-6 injection (data not shown).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Strength:plain· not yet calibratedCausal:direct· 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
“SOCS-3 protein can be detected after IL-6 injection, but not after TNF injection (Figure 6c).”
§ Expression of suppressors of cytokine signaling during liver regeneration > IL-6 injection induces SOCS-3 mRNA in TNF-R1-and IL-6 KO mice.
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
“Moreover, SOCS-3 protein was detected in WT by immunoblot analysis, but not in IL-6 KO liver (Figure 3c).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Blunted induction of SOCS-3 in IL-6 KO mice after PH.
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
“Moreover, both hepatocytes in vivo and in culture respond to IL-6 treatment in a similar manner; that is, only STAT-3 homodimers (SIF A) are found (unpublished observations and ref. 30).”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Not checked — no full text of the sourcecites [30] Bode, 1999, FEBS Lett source
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
“PH induced CIS and SOCS-2 levels only between fourfold and tenfold compared with controls, and in some experiments no induction was detected.”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
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
“A 40-to 50-fold increase of SOCS-3 mRNA is seen at 2 hours and is sustained for 4 hours when the levels start declining at 8 hours after PH and return to baseline levels by 24 hours (Figure 2b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“To date, there are several mechanisms known to be involved in inactivating STAT pathways: the SH2-containing protein tyrosine phosphatases, SHP-1 and -2, the protein inhibitors of activated STATs (PIAS), and the suppressors of cytokine signaling (SOCS) (reviewed in refs.4,[17][18][19].”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
- Not matchedcites reviewed in refs.4,[17][18][19]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:boosted· 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.
- Not matched
In the paper
“Depending on the tissue or cell type, the mRNA is short lived and the half-life of the SOCS protein is between 1 to 2 hours (23).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
- Not checked — no full text of the sourcecites [23] Siewert, 1999, Eur J Biochem 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.
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
“It has been demonstrated previously that STAT-3 is activated after PH as the result of increased IL-6 levels (8, 9, 16), implicating both IL-6 and STAT-3 as part of the priming mechanism for hepatocyte proliferation.”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It 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
“Thus, STAT-3 tyrosine 705 phosphorylation and DNA-binding activity are transiently activated after surgery.”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH activates STAT-3 in a transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Preoperative injection of IL-6 not only rescues the defects in hepatocyte proliferation, but returns a number of early signal transduction pathways to levels seen in wild-type (WT) mice (9).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
What the sources say
- Not checked — no full text of the sourcecites [9] Cressman, 1996, Science source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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
“For regeneration to take place, normally quiescent hepatocytes must gain proliferative capacity and undergo a transition from G0 to G1, a process known as priming (1,6).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Introduction
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Specific STAT-3 binding was analyzed by supershift analysis with a specific STAT-3 Ab, and competition with a 200-fold excess of unlabeled probe confirmed that only STAT-3 bound to the SIE probe (Figure 4b).”
§ Expression of suppressors of cytokine signaling during liver regeneration > Defective induction of STAT-3 in IL-6 KO mice after PH.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ 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
“Thus, PH appears to selectively upregulate SOCS-3 and not other members of the SOCS family.”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ 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
“Importantly, the induction of SOCS-3 correlates with the activation and inactivation of STAT-3, suggesting that in liver regeneration SOCS-3 participates in a negative-feedback loop to decrease STAT-3 activity.”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The STAT family of transcription factors mediates the induction of SOCS genes.
- Rests on an assumption: SOCS proteins participate in a feedback loop to inhibit STAT activity as well as cytokine signals.
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
“Taken together, these results indicate that SOCS-3 is the major SOCS family member induced after PH, and the induction of SOCS-3 mRNA and protein levels is transient.”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ 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
“In summary, IL-6 injection bypasses the lack of TNF and IL-6 signaling and induces all SOCS molecules examined in murine liver.”
§ Expression of suppressors of cytokine signaling during liver regeneration > IL-6 injection induces SOCS-3 mRNA in TNF-R1-and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“SOCS mRNA levels were normalized to cyclophilin levels at each time point.”
§ Expression of suppressors of cytokine signaling during liver regeneration > RNA preparation and Northern analysis.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The blots were stripped and reprobed with β-actin to ensure equal loading (Figure 2c, bottom).”
§ Expression of suppressors of cytokine signaling during liver regeneration > PH induces SOCS-3 in a robust and transient manner.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“These results suggest that SOCS-3 induction is dependent on IL-6 and, perhaps, TNF-signaling pathways.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Laparotomy was performed as the sham operation, otherwise the sham-operated mice were treated the same as PH mice.”
§ Expression of suppressors of cytokine signaling during liver regeneration > Animals.
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.
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
“These results suggest that while TNF can induce SOCS-3, this induction is much weaker and more transient compared with the induction following PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > TNF injection induces SOCS-3 in WT, but not in TNF-R1 and IL-6 KO mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Other mechanisms such as PIAS (39) that downregulate cytokine signaling in other cells may also play a role in inhibiting early cytokine signaling during PH.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
What the sources say
- Not checked — no full text of the sourcecites [39] Shuai, 2000, Oncogene 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.
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
“Secondly, existing, activated pools of STAT-3 (i.e., tyrosine phosphorylated) may be inactivated by dephosphorylation through the actions of a tyrosine phosphatase.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
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.
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 priming phase of hepatocyte replication probably ends at 5-6 hours after PH, perhaps even earlier.”
§ Expression of suppressors of cytokine signaling during liver regeneration > 1290
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
The paper relies on this without support.
The STAT family of transcription factors mediates the induction of SOCS genes.
“Importantly, the STAT family of transcription factors mediates the induction of SOCS genes.”
The paper relies on this without support.
SOCS proteins participate in a feedback loop to inhibit STAT activity as well as cytokine signals.
“Thus, SOCS proteins participate in a feedback loop to inhibit STAT activity as well as cytokine signals.”
The paper relies on this without support.
The mechanisms that downregulate or turn off the cytokine signaling pathways during liver regeneration are unclear.
“However, the mechanisms that downregulate or”
The paper relies on this without support.
TNF levels increase after PH, activating NF-kappaB, which upregulates IL-6 mRNA, resulting in elevated serum levels of IL-6.
“TNF levels increase after PH, activating the transcription factor, NF-κB, which in turn upregulates IL-6 mRNA, resulting in elevated serum levels of IL-6.”
The paper relies on this without support.
IL-6 stimulates hepatic STAT-3 by inducing phosphorylation at tyrosine 705, which allows nuclear translocation and DNA binding.
“IL-6 stimulates hepatic STAT-3 by inducing phosphorylation at tyrosine 705, which allows nuclear translocation and DNA binding.”
The paper relies on this without support.
STAT-3 induces SOCS-3 mRNA, leading to an increase in SOCS-3 protein levels, which downregulate IL-6-stimulated STAT-3.
“STAT-3 also induces SOCS-3 mRNA leading to an increase in SOCS-3 protein levels, which downregulate IL-6-stimulated STAT-3.”
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.
SOCS-3 protein is both present and absent at 8 hours
MinorThe results describe sustained SOCS-3 protein expression through 8 and 10 hours after PH, whereas the discussion says it is no longer detectable by 8 hours.
“Increased SOCS-3 protein levels were first detected by 2 hours with sustained expression until 8 and 10 hours (Figure 2c, top).”
“Both STAT-3 activity and SOCS-3 protein are no longer detectable by 8 hours after PH.”
Figure 5 caption contradicts CIS induction in IL-6 KO mice
MinorThe caption says TNF induces neither SOCS-3 nor CIS in IL-6 KO liver, but the results state that CIS is induced in those mice.
“TNF injection induces SOCS-3 and CIS mRNA in a time-dependent manner in WT, but not in TNF-R1 KO and IL-6 KO mouse liver.”
“In contrast to SOCS-3, CIS is induced in the liver of IL-6 KO mice but not in TNF-R1 KO mice.”
STAT-3 serine phosphorylation site differs between methods and results
MinorThe methods identify an antibody against STAT-3 phosphoserine 729, but the results identify the measured signal as phosphorylation of serine 727.
“anti-phosphotyrosine 705 and anti-phosphoserine 729 STAT-3 Ab's (9131 and 9134, respectively)”
“Phosphorylation of serine 727 of STAT-3 can be weakly detected (Figure 1a, middle), but the signal is variable.”
Citations
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Self-citation
Flagged first, then by citations
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Sorted by citations
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“pl?O14543">SOCS3 , which correlates with the subsequent downregulation of phosphorylated STAT3, thereby terminating the IL-6 signa”
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Self-citationSOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2
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“Interestingly, recent evidence suggests that some of the observed effects of TNF- may be mediated by its ability to induce IL-6 and IL-6 receptor expression in tissues such as the liver and muscle (38,39).”
BackgroundSOCS3 negatively regulates IL-6 signaling in vivo
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Metadata
- Authors
- Campbell, J. S., Prichard, L., Schaper, F., Schmitz, J., Stephenson-Famy, A., Rosenfeld, M. E., Argast, G. M., Heinrich, P. C., & Fausto, N.
- Affiliations
- University of Washington (US)
- RWTH Aachen University (DE)
- Corresponding author
- Fausto, Nelson
- Venue
- Journal of Clinical Investigation
- Published
- 2001-05-15
- Volume
- 107
- Issue
- 10
- Pages
- 1285-1292
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC209297
- OpenAlex
- W2013349369
- Cited by
- 156
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2019: 4 · 2018: 2 · 2017: 8 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 9 · 2012: 9
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health (1r43ai023226-01, CA23226)
- National Cancer Institute (R01 CA074131, R37 CA023226, CA 74131, R01CA023226)
- National Institute of Allergy and Infectious Diseases (AI-23226)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32 DK09920-01, F32DK009920)
- National Institute of Environmental Health Sciences (T32-ES07032-23, T32ES007032)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- suppressor of cytokine signaling, SOCS3, SOCS1, SOCS2, liver regeneration, partial hepatectomy, interleukin-6, TNF-α, STAT3 signaling, tyrosine phosphorylation, IL-6 knockout mice, TNF receptor 1
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Animals, DNA-Binding Proteins, Gene Expression Regulation, Hepatectomy, Liver Regeneration, Proteins, Repressor Proteins, Transcription Factors, Tumor Necrosis Factor-alpha, Signal Transduction, Trans-Activators, Antigens, CD, Interleukin-6, Receptors, Tumor Necrosis Factor, Mice, Knockout, Receptors, Tumor Necrosis Factor, Type I, STAT3 Transcription Factor, Suppressor of Cytokine Signaling Proteins, Mice
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