ArticleHepatology (Baltimore, Md.)2013
A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 134 citations in OpenAlex.
- A subset of hepatic fibroblasts marked by Gli1 expression generates portal fibrosis and promotes ductular reaction.JHEP reports : innovation in hepatology · 2026Article
- ECM1 produced by hepatic stellate cells serves as a gatekeeper of liver homeostasis in hepatic fibrosis.Hepatology (Baltimore, Md.) · 2026Article
- <p>Beyond hepatic stellate cell heterogeneity: Resolving fibrosis, restoring regeneration (Review)</p>.International journal of molecular medicine · 2026Review
- Immune-Centered Cross-Talk Between Cancer Cells and the Tumor Microenvironment-Implications for Therapy.Cancers · 2026Review
- Global Trends in Hepatocellular Carcinoma and TGF-β Research: A Bibliometric and Visualization Analysis from 2000 to 2024.Current protein & peptide science · 2026Article
- The Sugar-Coated Truth of Alcohol-Associated Liver Disease: Galectins as Multifaceted Regulators of Alcohol-Induced Liver Injury.The American journal of pathology · 2026Review
- Regulation of Hepatic Stellate Cell Phenotypes in Metabolic Dysfunction-Associated Steatohepatitis.Gastroenterology · 2025Review
- Biomimetic nanoparticles for targeted therapy of liver disease.RSC pharmaceutics · 2025Review
- Hepatic stellate cell-specific Kcnma1 deletion mitigates metabolic dysfunction-associated steatotic liver disease progression via upregulating Amphiregulin secretion.Molecular metabolism · 2025Article
- Hepatic stellate cells: balancing homeostasis, hepatoprotection and fibrogenesis in health and disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Article
- Cross-Talk Between Tumor Cells and Stellate Cells Promotes Oncolytic VSV Activity in Intrahepatic Cholangiocarcinoma.Cancers · 2025Article
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Found in translation-Fibrosis in metabolic dysfunction-associated steatohepatitis (MASH).Science translational medicine · 2023Review
- Friend or foe? The elusive role of hepatic stellate cells in liver cancer.Nature reviews. Gastroenterology & hepatology · 2023Review
- Fibroblasts in liver cancer: functions and therapeutic translation.The lancet. Gastroenterology & hepatology · 2023Review
- Hepatic stellate cells maintain liver homeostasis through paracrine neurotrophin-3 signaling that induces hepatocyte proliferation.Science signaling · 2023Article
- The origins, roles and therapies of cancer associated fibroblast in liver cancer.Frontiers in oncology · 2023Review
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31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledWe have developed a novel model for depleting mouse hepatic stellate cells (HSCs) that has allowed us to clarify their contributions to hepatic injury and fibrosis. Transgenic (Tg) mice expressing the herpes simplex virus thymidine kinase gene (HSV-Tk) driven by the mouse GFAP promoter were used to render proliferating HSCs susceptible to killing in response to ganciclovir (GCV). Effects of GCV were explored in primary HSCs and in vivo. Panlobular damage was provoked to maximize HSC depletion by combining CCl(4) (centrilobular injury) with allyl alcohol (AA) (periportal injury), as well as in a bile duct ligation (BDL) model. Cell depletion in situ was quantified using dual immunofluorescence (IF) for desmin and GFAP. In primary HSCs isolated from both untreated wild-type (WT) and Tg mice, GCV induced cell death in ≈ 50% of HSCs from Tg, but not WT, mice. In TG mice treated with CCl(4) +AA+GCV, there was a significant decrease in GFAP and desmin-positive cells, compared to WT mice (≈ 65% reduction; P < 0.01), which was accompanied by a decrease in the expression of HSC-activation markers (alpha smooth muscle actin, beta platelet-derived growth factor receptor, and collagen I). Similar results were observed after BDL. Associated with HSC depletion in both fibrosis models, there was marked attenuation of fibrosis and liver injury, as indicated by Sirius Red/Fast Green, hematoxylin and eosin quantification, and serum alanine/aspartate aminotransferase. Hepatic expression of interleukin-10 and interferon-gamma was increased after HSC depletion. No toxicity of GCV in either WT or Tg mice accounted for the differences in injury.
conclusionActivated HSCs significantly amplify the response to liver injury, further expanding this cell type's repertoire in orchestrating hepatic injury and repair.
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Registered trials
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.