ArticleHepatology (Baltimore, Md.)2016
Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis.
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 63 papers.
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Who cites it
63 citing papers in PubMed, 104 citations in OpenAlex.
- Fibrocystin/polyductin (FPC): new functional insights into ARPKD pathogenesis revealed by informatics, comparative genomics, and model systems.Pediatric nephrology (Berlin, Germany) · 2026Review
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- Molecular PET imaging of integrin αvβ6 reveals biliary and fibrotic changes in preclinical MASH.Biomarker research · 2026Article
- P-STAT3-dependent SPP1 transcription in cholangiocytes drives hepatic stellate cells activation in congenital hepatic fibrosis.Communications biology · 2026Article
- Targeting Prolyl 3-hydroxylase 1 inhibits pancreatic cancer progression and macrophage immunity.Nature communications · 2026Article
- Histological, ultrastructural, and single-cell profiling reveal immune-mediated remodeling in gallbladder inflammation.Cell and tissue research · 2026Article
- Therapeutic potential of tetrahydroxylated bile acids in reducing liver injury: Insights from thePediatric investigation · 2026Article
- Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025Review
- Management of intrahepatic cholangiocarcinoma in a patient with Caroli's disease: a case report and literature review.Journal of surgical case reports · 2025Article
- Review
- Multi-omics analysis of host-microbiome interactions in a mouse model of congenital hepatic fibrosis.BMC microbiology · 2025Article
- Primary sclerosing cholangitis.Nature reviews. Disease primers · 2025Review
- Purinergic signaling and cholangiocyte regeneration: a new frontier in ischemic liver injury.Frontiers in transplantation · 2025Review
- The beneficial health effects of puerarin in the treatment of cardiovascular diseases: from mechanisms to therapeutics.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Heritable Chronic Cholestatic Liver Diseases: A Review.Journal of clinical and translational hepatology · 2024Review
- ZFYVE19 deficiency: a ciliopathy involving failure of cell division, with cell death.Journal of medical genetics · 2024Article
- Knockout of integrin αvβ6 protects against renal inflammation in chronic kidney disease by reduction of pro-inflammatory macrophages.Cell death & disease · 2024Article
- [A case of neonatal liver failure].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Article
- Harnessing metabolism of hepatic macrophages to aid liver regeneration.Cell death & disease · 2023Review
- Two-Pore-Domain Potassium Channel TREK-1 Mediates Pulmonary Fibrosis through Macrophage M2 Polarization and by Direct Promotion of Fibroblast Differentiation.Biomedicines · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
unlabelledCongenital hepatic fibrosis (CHF) is a disease of the biliary epithelium characterized by bile duct changes resembling ductal plate malformations and by progressive peribiliary fibrosis, in the absence of overt necroinflammation. Progressive liver fibrosis leads to portal hypertension and liver failure; however, the mechanisms leading to fibrosis in CHF remain elusive. CHF is caused by mutations in PKHD1, a gene encoding for fibrocystin, a ciliary protein expressed in cholangiocytes. Using a fibrocystin-defective (Pkhd1(del4/del4)) mouse, which is orthologous of CHF, we show that Pkhd1(del4/del4) cholangiocytes are characterized by a β-catenin-dependent secretion of a range of chemokines, including chemokine (C-X-C motif) ligands 1, 10, and 12, which stimulate bone marrow-derived macrophage recruitment. We also show that Pkhd1(del4/del4) cholangiocytes, in turn, respond to proinflammatory cytokines released by macrophages by up-regulating αvβ6 integrin, an activator of latent local transforming growth factor-β1. While the macrophage infiltrate is initially dominated by the M1 phenotype, the profibrogenic M2 phenotype increases with disease progression, along with the number of portal myofibroblasts. Consistent with these findings, clodronate-induced macrophage depletion results in a significant reduction of portal fibrosis and portal hypertension as well as of liver cysts.
conclusionFibrosis can be initiated by an epithelial cell dysfunction, leading to low-grade inflammation, macrophage recruitment, and collagen deposition; these findings establish a new paradigm for biliary fibrosis and represent a model to understand the relationship between cell dysfunction, parainflammation, liver fibrosis, and macrophage polarization over time.
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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.