ArticleJournal of hepatology2013
IFN-γ inhibits liver progenitor cell proliferation in HBV-infected patients and in 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-fed mice.
Article in Journal of hepatology, 2013. 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, 38 citations in OpenAlex.
- TGF-β serves as a critical signaling determinant of liver progenitor cell activation and function.The Journal of clinical investigation · 2026Article
- Causal Effects of a Hepatic Senescence Gene Set on MASLD Fibrosis: A Mendelian Randomization Study and Quercetin Molecular Docking Analysis.Biomedicines · 2026Article
- ERG mediates the differentiation of hepatic progenitor cells towards immunosuppressive PDGFRαCell death & disease · 2025Article
- Comparative single-cell landscape of immune cells in human livers affected HBV and non-viral cirrhosis.Frontiers in medicine · 2025Article
- Metabolism of hepatic stellate cells in chronic liver diseases: emerging molecular and therapeutic interventions.Theranostics · 2025Review
- Key role of interferon regulatory factor 1 (IRF-1) in regulating liver disease: progress and outlook.Journal of Zhejiang University. Science. B · 2024Review
- Review: Advances in the Pathogenesis and Treatment of Immune Thrombocytopenia Associated with Viral Hepatitis.Global medical genetics · 2023Review
- IFN-γ: A Crucial Player in the Fight Against HBV Infection?Immune network · 2023Review
- Ductular reaction in non-alcoholic fatty liver disease: When Macbeth is perverted.World journal of hepatology · 2023Review
- Mechanisms of esophageal stricture after extensive endoscopic resection: a transcriptomic analysis.Endoscopy international open · 2023Article
- Update on Hepatobiliary Plasticity.Seminars in liver disease · 2023Article
- The antifibrotic role of natural killer cells in liver fibrosis.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Protective Effects of Bee Venom-Derived Phospholipase ABiomedicines · 2021Article
- Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model.International journal of molecular sciences · 2021Article
- Myofibroblasts: Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis.Biomolecules · 2021Review
- Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocarcinoma.BMC gastroenterology · 2020Article
- Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts constitutes the hepatocarcinogenesis-associated microenvironment.Cell death and differentiation · 2020Article
- Interferon-γ enhances the antifibrotic effects of pirfenidone by attenuating IPF lung fibroblast activation and differentiation.Respiratory research · 2019Article
- Immune suppression in chronic hepatitis B infection associated liver disease: A review.World journal of gastroenterology · 2019Review
- Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC-induced cholestatic liver injury.Liver international : official journal of the International Association for the Study of the Liver · 2018Article
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Authors and funding
19 authors at 10 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsProliferation of liver progenitor cells (LPCs) is associated with inflammation and fibrosis in chronic liver diseases. However, how inflammation and fibrosis affect LPCs remains obscure.
methodsWe examined the role of interferon (IFN)-γ, an important pro-inflammatory and anti-fibrotic cytokine, in LPC expansion in HBV-infected patients and in mice challenged with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)- or choline-deficient, ethionine-supplemented (CDE) diet as well as in primary LPCs and LPC cell line.
resultsThe CK19 staining scores correlated with inflammation and fibrosis grades in the livers from 110 HBV-infected patients. Nine-month IFN-γ treatment decreased LPC numbers, inflammation, and fibrosis in these HBV-infected patients. Similarly, a two-week IFN-γ treatment also decreased LPC activation in DDC-treated mice. Disruption of IFN-γ or its signaling components (e.g., IFNGR, STAT1, and IRF-1) increased LPC proliferation and liver fibrosis in DDC-fed mice. In contrast, deletion of IFN-γ did not increase, but rather slightly reduced LPC proliferation in CDE-fed mice. In vitro, IFN-γ attenuated proliferation of the LPC cell line BMOL and of primary LPCs from wild type mice, but not STAT1(-/-) or IRF-1(-/-) mice. Furthermore, co-culture assays suggest that IFN-γ can indirectly promote LPC proliferation via the activation of macrophages but attenuate it via the inhibition of hepatic stellate cells.
conclusionsIFN-γ inhibits LPC expansion via the direct inhibition of LPC proliferation and indirect attenuation of liver fibrosis in the DDC model, but it may also enhance LPC expansion via the promotion of inflammation in the CDE model; thereby playing dual roles in regulating LPC proliferation in vivo.
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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.