ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Activation of the renin-angiotensin system stimulates biliary hyperplasia during cholestasis induced by extrahepatic bile duct ligation.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Sildenafil blunts cholestasis-associated cholemic nephropathy in a rat model of bile duct ligation.Clinical and experimental hepatology · 2025Article
- Application of PPAR Ligands and Nanoparticle Technology in Metabolic Steatohepatitis Treatment.Biomedicines · 2024Review
- The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies.Cancer cell international · 2023Review
- Angiotensin II type 1 receptor localizes at the blood-bile barrier in humans and pigs.Histochemistry and cell biology · 2022Article
- Metformin alleviates cholestasis-associated nephropathy through regulating oxidative stress and mitochondrial function.Liver research (Beijing, China) · 2021Article
- Mitigation of cholestasis-associated hepatic and renal injury by edaravone treatment: Evaluation of its effects on oxidative stress and mitochondrial function.Liver research (Beijing, China) · 2021Article
- Silymarin mitigates bile duct obstruction-induced cholemic nephropathy.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis.World journal of gastroenterology · 2021Article
- Review
- The Role of High Fat Diets and Liver Peptidase Activity in the Development of Obesity and Insulin Resistance in Wistar Rats.Nutrients · 2020Article
- Blockade of the renin-angiotensin system suppresses hydroxyl radical production in the rat striatum during carbon monoxide poisoning.Scientific reports · 2020Article
- Biliary epithelium: A neuroendocrine compartment in cholestatic liver disease.Clinics and research in hepatology and gastroenterology · 2018Review
- Mechanisms of cholangiocyte responses to injury.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
- Synthetic Receptors Induce Anti Angiogenic and Stress Signaling on Human First Trimester Cytotrophoblast Cells.International journal of environmental research and public health · 2017Article
- Novel treatment options for portal hypertension.Gastroenterology report · 2017Article
- The Neuropeptide Galanin Is Up-Regulated during Cholestasis and Contributes to Cholangiocyte Proliferation.The American journal of pathology · 2017Article
- Regulators of Cholangiocyte Proliferation.Gene expression · 2017Review
- The characteristics of activated portal fibroblasts/myofibroblasts in liver fibrosis.Differentiation; research in biological diversity · 2016Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Cholangiocyte proliferation is regulated in a coordinated fashion by many neuroendocrine factors through autocrine and paracrine mechanisms. The renin-angiotensin system (RAS) is known to play a role in the activation of hepatic stellate cells and blocking the RAS attenuates hepatic fibrosis. We investigated the role of the RAS during extrahepatic cholestasis induced by bile duct ligation (BDL). In this study, we used normal and BDL rats that were treated with control, angiotensin II (ANG II), or losartan for 2 wk. In vitro studies were performed in a primary rat cholangiocyte cell line (NRIC). The expression of renin, angiotensin-converting enzyme, angiotensinogen, and angiotensin receptor type 1 was evaluated by immunohistochemistry (IHC), real-time PCR, and FACs and found to be increased in BDL compared with normal rat. The levels of ANG II were evaluated by ELISA and found to be increased in serum and conditioned media of cholangiocytes from BDL compared with normal rats. Treatment with ANG II increased biliary mass and proliferation in both normal and BDL rats. Losartan attenuated BDL-induced biliary proliferation. In vitro, ANG II stimulated NRIC proliferation via increased intracellular cAMP levels and activation of the PKA/ERK/CREB intracellular signaling pathway. ANG II stimulated a significant increase in Sirius red staining and IHC for fibronectin that was blocked by angiotensin receptor blockade. In vitro, ANG II stimulated the gene expression of collagen 1A1, fibronectin 1, and IL-6. These results indicate that cholangiocytes express a local RAS and that ANG II plays an important role in regulating biliary proliferation and fibrosis during extraheptic cholestasis.
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Registered trials
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