ArticleJournal of hepatology2023
GARP on hepatic stellate cells is essential for the development of liver fibrosis.
Article in Journal of hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- The circadian clock controls hepatic stellate cell activation via a BMAL1/CK1ε/REV-ERBα/transgelin signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Human single-cell atlas of proliferative diabetic retinopathy reveals a SOX15-overexpressing stromal population driving retinal fibrosis through the endothelin-1 -EDNRB axis.Journal of translational medicine · 2026Article
- AURKA regulates HBV-induced hepatic stellate cell inflammation and liver fibrosis by modulating K48-linked ubiquitination and proteasomal degradation of TLR3.Journal of bioenergetics and biomembranes · 2026Article
- NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Residual bile flow shapes PPARγ-mediated antifibrotic responses in experimental segmental cholestasis.Scientific reports · 2026Article
- Macrophage β-catenin-Ihh axis induces hepatic stellate cell activation and fibrosis in metabolic dysfunction-associated steatohepatitis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Selective blockade of latent TGF-β1 activation suppresses tissue fibrosis with good safety.Communications medicine · 2026Article
- Ferroptosis in metabolic dysfunction-associated steatotic liver disease.Frontiers in immunology · 2026Review
- Exploring the roles of genes associated with leukocyte transendothelial migration in liver cirrhosis development.PloS one · 2026Article
- Mucosal immunity in cancer metastasis: roles, mechanisms, and therapeutic implications.Frontiers in immunology · 2026Review
- Cancer cells metastasize in several types of cancer via two distinct routes, probably based on mechanical signals.Frontiers in cell and developmental biology · 2026Review
- Tumor-Derived Interleukin 35 Promotes Fibrosis in the Tumor Microenvironment of Pancreatic Cancer by Activating Pancreatic Stellate Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tissue-resident memory CD8Nature reviews. Gastroenterology & hepatology · 2025Review
- The Involvement of Endothelin-1 in Sepsis and Organ Dysfunction-A Novel Biomarker in Patient Assessment.Biomedicines · 2025Review
- NSun2-Mediated tsRNAs Alleviate Liver Fibrosis via FAK Dephosphorylation.Cell proliferation · 2025Article
- The role of tetraspanins in organ fibrosis: mechanisms and therapeutic perspectives.Journal of translational medicine · 2025Review
- GARP-expressing Tregs as a source of immunosuppressive TGF-β1 in human tumors.Cancer immunology, immunotherapy : CII · 2025Article
- The Immune Microenvironment: New Therapeutic Implications in Organ Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Pantothenic acid ameliorates hepatic fibrosis by targeting IGFBP6 to regulate the TGF-β/SMADs pathway.Communications biology · 2025Article
- Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsGlycoprotein A repetitions predominant (GARP) is a membrane protein that functions as a latent TGF-β docking molecule. While the immune regulatory properties of GARP on blood cells have been studied, the function of GARP on tissue stromal cells remains unclear. Here, we investigate the role of GARP expressed on hepatic stellate cells (HSCs) in the development of liver fibrosis.
methodsThe function of GARP on HSCs was explored in toxin-induced and metabolic liver fibrosis models, using conditional GARP-deficient mice or a newly generated inducible system for HSC-specific gene ablation. Primary mouse and human HSCs were isolated to evaluate the contribution of GARP to the activation of latent TGF-β. Moreover, cell contraction of HSCs in the context of TGF-β activation was tested in a GARP-dependent fashion.
resultsMice lacking GARP in HSCs were protected from developing liver fibrosis. Therapeutically deleting GARP on HSCs alleviated the fibrotic process in established disease. Furthermore, natural killer T cells exacerbated hepatic fibrosis by inducing GARP expression on HSCs through IL-4 production. Mechanistically, GARP facilitated fibrogenesis by activating TGF-β and enhancing endothelin-1-mediated HSC contraction. Functional GARP was expressed on human HSCs and significantly upregulated in the livers of patients with fibrosis. Lastly, deletion of GARP on HSCs did not augment inflammation or liver damage.
conclusionsGARP expressed on HSCs drives the development of liver fibrosis via cell contraction-mediated activation of latent TGF-β. Considering that systemic blockade of TGF-β has major side effects, we highlight a therapeutic niche provided by GARP and surface-mediated TGF-β activation. Thus, our findings suggest an important role of GARP on HSCs as a promising target for the treatment of liver fibrosis. IMPACT AND IMPLICATIONS: Liver fibrosis represents a substantial and increasing public health burden globally, for which specific treatments are not available. Glycoprotein A repetitions predominant (GARP) is a membrane protein that functions as a latent TGF-β docking molecule. Here, we show that GARP expressed on hepatic stellate cells drives the development of liver fibrosis. Our findings suggest GARP as a novel target for the treatment of fibrotic disease.
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