ArticleHepatology (Baltimore, Md.)2016
Integrin αvβ6 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The trial behind it
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Who cites it
66 citing papers in PubMed, 114 citations in OpenAlex.
- Molecular PET imaging of integrin αvβ6 reveals biliary and fibrotic changes in preclinical MASH.Biomarker research · 2026Article
- A novel cell-permeable LOXL2 inhibitor PAT-1251 potently suppresses biliary liver fibrosis via collagen crosslinking-dependent and -independent mechanisms.Hepatology communications · 2026Article
- Dissecting the mechanisms of MASLD fibrosis in the era of single-cell and spatial omics.The Journal of clinical investigation · 2025Review
- Intestinal mast cell-derived leukotrienes mediate the anaphylactic response to ingested antigens.Science (New York, N.Y.) · 2025Article
- Anti-integrin αvβ6 Autoantibodies Are Increased in Primary Sclerosing Cholangitis Patients With Concomitant Inflammatory Bowel Disease and Correlate With Liver Disease Severity.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2025Article
- An integrin-based quercetin 7-rhamnoside liver-targeted delivery liposomes for intrahepatic cholestasis in pregnancy.Materials today. Bio · 2025Article
- Clinical management of autoimmune liver diseases: juncture, opportunities, and challenges ahead.Immunologic research · 2025Review
- Microenvironmental control of the ductular reaction: balancing repair and disease progression.Cell death & disease · 2025Review
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
- Mechanosignaling via Integrins: Pivotal Players in Liver Fibrosis Progression and Therapy.Cells · 2025Review
- Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells byFrontiers in pharmacology · 2025Article
- Integrin subunit beta 6 is a potential diagnostic marker for acute kidney injury in patients with diabetic kidney disease: a single cell sequencing data analysis.Renal failure · 2024Article
- Liver Fibrosis: From Basic Science towards Clinical Progress, Focusing on the Central Role of Hepatic Stellate Cells.International journal of molecular sciences · 2024Review
- Article
- Hepatic progenitor cell-originated ductular reaction facilitates liver fibrosis through activation of hedgehog signaling.Theranostics · 2024Article
- The Interplay between Integrins and Immune Cells as a Regulator in Cancer Immunology.International journal of molecular sciences · 2023Review
- Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Article
- Cholangiokines: undervalued modulators in the hepatic microenvironment.Frontiers in immunology · 2023Review
- Heme oxygenase-1 mitigates liver injury and fibrosis via modulation of LNX1/Notch1 pathway in myeloid cells.iScience · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
unlabelledIntegrin αvβ6 is rapidly up-regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGFβ1). In human liver cirrhosis, αvβ6 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that αvβ6 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function in vivo and in vitro through integrin αvβ6-dependent TGFβ1 activation. Freshly isolated αvβ6(+) liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes in vitro, whereas colony formation by epithelial cell adhesion molecule-positive progenitor cells is blocked by αvβ6-neutralizing antibody and in integrin beta 6-deficient cells. Inhibition of progenitors by anti-αvβ6 antibody is recapitulated by TGFβ1 neutralization and rescued by addition of bioactive TGFβ1. Genetic disruption or selective targeting of αvβ6 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction.
conclusionThese results suggest that αvβ6 is a promising target for chronic fibrotic liver diseases and associated cancers.
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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.