ArticleThe Journal of clinical investigation2021
Bile acid-activated macrophages promote biliary epithelial cell proliferation through integrin αvβ6 upregulation following liver injury.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression.Nature communications · 2023Pooled it
- Molecular PET imaging of integrin αvβ6 reveals biliary and fibrotic changes in preclinical MASH.Biomarker research · 2026Article
- Bile acid retention in efferocytic macrophages shapes their inflammatory status during cholangitis.The Journal of experimental medicine · 2026Article
- Unveiling a novel macrophage-driven mechanism for obeticholic acid-induced liver injury in cholestatic: targeting NLRP12Cell biology and toxicology · 2026Article
- Histological, ultrastructural, and single-cell profiling reveal immune-mediated remodeling in gallbladder inflammation.Cell and tissue research · 2026Article
- Mesenchymal stromal cell administration promotes macrophage-mediated bile duct regeneration.Regenerative therapy · 2026Article
- Integrating single-cell and bulk RNA sequencing data reveals RGS4 as a functional driver in a proliferative subgroup of SF-1 lineage PitNETs.Frontiers in cell and developmental biology · 2026Article
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Antimicrobial and healing efficacy of bile salts with insights into cytotoxic activity.Scientific reports · 2025Article
- Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells.Cellular & molecular immunology · 2025Review
- Central role for cholangiocyte pathobiology in cholestatic liver diseases.Hepatology (Baltimore, Md.) · 2025Review
- Dissecting the mechanisms of MASLD fibrosis in the era of single-cell and spatial omics.The Journal of clinical investigation · 2025Review
- Article
- An integrin-based quercetin 7-rhamnoside liver-targeted delivery liposomes for intrahepatic cholestasis in pregnancy.Materials today. Bio · 2025Article
- The Cardiohepatic Axis in Heart Failure.JACC. Basic to translational science · 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
- Purinergic signaling and cholangiocyte regeneration: a new frontier in ischemic liver injury.Frontiers in transplantation · 2025Review
- Bile acids and gestational diabetes mellitus: exploring the link and implications - a review.Frontiers in endocrinology · 2025Review
- The dual role of neutrophils in sepsis-associated liver injury.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Cholangiopathies caused by biliary epithelial cell (BEC) injury represent a leading cause of liver failure. No effective pharmacologic therapies exist, and the underlying mechanisms remain obscure. We aimed to explore the mechanisms of bile duct repair after targeted BEC injury. Injection of intermedilysin into BEC-specific human CD59 (hCD59) transgenic mice induced acute and specific BEC death, representing a model to study the early signals that drive bile duct repair. Acute BEC injury induced cholestasis followed by CCR2+ monocyte recruitment and BEC proliferation. Using microdissection and next-generation RNA-Seq, we identified 5 genes, including Mapk8ip2, Cdkn1a, Itgb6, Rgs4, and Ccl2, that were most upregulated in proliferating BECs after acute injury. Immunohistochemical analyses confirmed robust upregulation of integrin αvβ6 (ITGβ6) expression in this BEC injury model, after bile duct ligation, and in patients with chronic cholangiopathies. Deletion of the Itgb6 gene attenuated BEC proliferation after acute bile duct injury. Macrophage depletion or Ccr2 deficiency impaired ITGβ6 expression and BEC proliferation. In vitro experiments revealed that bile acid-activated monocytes promoted BEC proliferation through ITGβ6. Our data suggest that BEC injury induces cholestasis, monocyte recruitment, and induction of ITGβ6, which work together to promote BEC proliferation and therefore represent potential therapeutic targets for cholangiopathies.
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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.