ArticleHepatology (Baltimore, Md.)2016
The secretin/secretin receptor axis modulates liver fibrosis through changes in transforming growth factor-β1 biliary secretion in mice.
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 65 papers.
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Who cites it
65 citing papers in PubMed, 102 citations in OpenAlex.
- The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.Disease models & mechanisms · 2026Review
- Mapping the hepatic neural niche: from three-dimensional innervation architecture to periportal interoception and human translation.Frontiers in physiology · 2026Review
- Microenvironmental control of the ductular reaction: balancing repair and disease progression.Cell death & disease · 2025Review
- MetALD: Clinical aspects, pathophysiology and treatment.JHEP reports : innovation in hepatology · 2025Review
- Clostridium Scindens Protects Against Vancomycin-Induced Cholestasis and Liver Fibrosis by Activating Intestinal FXR-FGF15/19 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The microenvironment in the development of MASLD-MASH-HCC and associated therapeutic in MASH-HCC.Frontiers in immunology · 2025Review
- Transposon-based oncogene integration in Abcb4(Mdr2)Journal of hepatology · 2025Article
- Unraveling the complexities of fibrosis and ductular reaction in liver disease: pathogenesis, mechanisms, and therapeutic insights.American journal of physiology. Cell physiology · 2024Review
- Costunolide alleviated DDC induced ductular reaction and inflammatory response in murine model of cholestatic liver disease.Journal of traditional and complementary medicine · 2023Article
- Knockout of secretin ameliorates biliary and liver phenotypes during alcohol-induced hepatotoxicity.Cell & bioscience · 2023Article
- Liver Regeneration and Immunity: A Tale to Tell.International journal of molecular sciences · 2023Review
- Cholangiokines: undervalued modulators in the hepatic microenvironment.Frontiers in immunology · 2023Review
- Cellular heterogeneity and plasticity during NAFLD progression.Frontiers in molecular biosciences · 2023Review
- Review
- Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis.Bioactive materials · 2022Article
- A Review of Molecular Interplay between Neurotrophins and miRNAs in Neuropsychological Disorders.Molecular neurobiology · 2022Review
- Developmental programming: Impact of prenatal bisphenol-A exposure on liver and muscle transcriptome of female sheep.Toxicology and applied pharmacology · 2022Article
- β-Caryophyllene Counteracts Chemoresistance Induced by Cigarette Smoke in Triple-Negative Breast Cancer MDA-MB-468 Cells.Biomedicines · 2022Article
- Liver secretin receptor predicts portoenterostomy outcomes and liver injury in biliary atresia.Scientific reports · 2022Article
- Gene Set Enrichment Analysis Detected Immune Cell-Related Pathways Associated with Primary Sclerosing Cholangitis.BioMed research international · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledThe secretin/secretin receptor (SR) axis is up-regulated by proliferating cholangiocytes during cholestasis. Secretin stimulates biliary proliferation by down-regulation of let-7a and subsequent up-regulation of the growth-promoting factor, nerve growth factor (NGF). It is not known whether the secretin/SR axis plays a role in subepithelial fibrosis observed during cholestasis. Our aim was to determine the role of the secretin/SR axis in activation of biliary fibrosis in animal models and human primary sclerosing cholangitis (PSC). Studies were performed in wild-type (WT) mice with bile duct ligation (BDL), BDL SR(-/-) mice, or Mdr2(-/-) mouse models of cholestatic liver injury. In selected studies, the SR antagonist (Sec 5-27) was used to block the secretin/SR axis. Biliary proliferation and fibrosis were evaluated as well as secretion of secretin (by cholangiocytes and S cells), expression of markers of fibrosis, transforming growth factor-β1 (TGF-β1), transforming growth factor-β1 receptor (TGF-β1R), let-7a, and downstream expression of NGF. Correlative studies were performed in human control and PSC liver tissue biopsies, serum, and bile. SR antagonist reduced biliary proliferation and hepatic fibrosis in BDL WT and Mdr2(-/-) mice. There was decreased expression of let-7a in BDL and Mdr2(-/-) cholangiocytes that was associated with increased NGF expression. Inhibition of let-7a accelerated liver fibrosis was attributed to cholestasis. There was increased expression of TGF-β1 and TGF-β1R. Significantly higher expression of secretin, SR, and TGF-β1 was observed in PSC patient liver samples compared to healthy controls. In addition, there was higher expression of fibrosis genes and remarkably decreased expression of let-7a and increased expression of NGF compared to the control.
conclusionThe secretin/SR axis plays a key role in regulating the biliary contribution to cholestasis-induced hepatic fibrosis. (Hepatology 2016;64:865-879).
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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.