ArticleThe American journal of pathology2010
Lack of glycoprotein 130/signal transducer and activator of transcription 3-mediated signaling in hepatocytes enhances chronic liver injury and fibrosis progression in a model of sclerosing cholangitis.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation.The Journal of clinical investigation · 2012Trial
- IL-22 modulates STAT3/β-catenin/let-7a signaling and hepatic granulomas in Schistosoma mansoni infection: versus praziquantel and combination treatment.Molecular biology reports · 2026Article
- Therapeutic potential of Janus kinase inhibitors for the management of fibrosis in inflammatory bowel disease.Journal of Crohn's & colitis · 2025Review
- The gp130/STAT3-endoplasmic reticulum stress axis regulates hepatocyte necroptosis in acute liver injury.Croatian medical journal · 2023Article
- Hepatocyte Specific gp130 Signalling Underlies APAP Induced Liver Injury.International journal of molecular sciences · 2022Article
- Tamoxifen Ameliorates Cholestatic Liver Fibrosis in Mice: Upregulation of TGFβ and IL6 Is a Potential Protective Mechanism.Biomedicines · 2022Article
- The palmitoyl acyltransferases ZDHHC5 and ZDHHC8 are uniquely present in DRG axons and control retrograde signaling via the Gp130/JAK/STAT3 pathway.The Journal of biological chemistry · 2020Article
- Inflammatory networks cultivate cancer cell metastasis to the liver.Cell cycle (Georgetown, Tex.) · 2020Article
- Dual TBK1/IKKɛ inhibitor amlexanox attenuates the severity of hepatotoxin-induced liver fibrosis and biliary fibrosis in mice.Journal of cellular and molecular medicine · 2020Article
- The STAT3 inhibitor S3I-201 suppresses fibrogenesis and angiogenesis in liver fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Luteolin-Mediated Inhibition of Hepatic Stellate Cell Activation via Suppression of the STAT3 Pathway.International journal of molecular sciences · 2018Article
- A novel scoring system based on common laboratory tests predicts the efficacy of TNF-inhibitor and IL-6 targeted therapy in patients with rheumatoid arthritis: a retrospective, multicenter observational study.Arthritis research & therapy · 2017Observational
- Catheterization of the gallbladder: A novel mouse model of severe acute cholangitis.World journal of gastroenterology · 2017Article
- Epidermal growth factor signaling protects from cholestatic liver injury and fibrosis.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Both MAPK and STAT3 signal transduction pathways are necessary for IL-6-dependent hepatic stellate cells activation.PloS one · 2017Article
- STAT3 Inhibition Suppresses Hepatic Stellate Cell Fibrogenesis: HJC0123, a Potential Therapeutic Agent for Liver Fibrosis.RSC advances · 2016Article
- Expression and activation of EGFR and STAT3 during the multistage carcinogenesis of intrahepatic cholangiocarcinoma induced by 3'-methyl-4 dimethylaminoazobenzene in rats.Journal of toxicologic pathology · 2015Article
- Animal Models for Fibrotic Liver Diseases: What We Have, What We Need, and What Is under Development.Journal of clinical and translational hepatology · 2015Review
- New Approaches for Studying Alcoholic Liver Disease.Current pathobiology reports · 2014Article
- STAT3 in hepatocellular carcinoma: new perspectives.Hepatic oncology · 2014Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model leads to chronic cholestatic liver injury and therefore resembles human diseases such as sclerosing cholangitis and forms of metabolic liver diseases. The role of the interleukin-6/glycoprotein 130 (gp130) system in this context is still undefined. Therefore, conditional gp130 knockout and knockin mice were used to achieve hepatocyte-specific deletions of gp130 (gp130(Deltahepa)), gp130-dependent ras (gp130(DeltahepaRas)), and signal transducer and activator of transcription (STAT) (gp130(DeltahepaSTAT)) activation. These mice were treated with a DDC-containing diet and analyzed over time. Mice deficient in hepatic gp130 and STAT signaling showed increased and earlier mortality than wild-type and gp130(DeltahepaRas) animals. Over time, significantly more apoptosis and cholestasis became evident in gp130(Deltahepa) and gp130(DeltahepaSTAT) mice. These mice also displayed increased tumor necrosis factor-alpha expression, a diminished acute-phase response (lack of STAT3 and serum amyloid A activation), and enhanced immune cell infiltration in the liver. These were associated with stronger periportal oval cell activation. In addition, DDC treatment in gp130(Deltahepa) and gp130(DeltahepaSTAT) mice resulted in significantly stronger hepatic stellate cell activation. Long-term analysis revealed the development of severe liver fibrosis in gp130(Deltahepa) and gp130(DeltahepaSTAT) animals, as evidenced by increased collagen accumulation. Here we demonstrate that gp130/STAT signaling in hepatocytes provides protection in a cholestatic hepatitis mouse model. STAT3-dependent signaling pathways in hepatocytes protect from apoptosis and tissue injury, which subsequently reduce oval cell activation and prevent fibrosis progression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.