ArticleLaboratory investigation; a journal of technical methods and pathology2012
Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms.
Article in Laboratory investigation; a journal of technical methods and pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 64 citations in OpenAlex.
- Histidine ammonia lyase expression characteristics in primary liver cancer: hepatocellular carcinoma and cholangiocarcinoma.Discover oncology · 2025Article
- Combination of H1 and H2 Histamine Receptor Antagonists: Current Knowledge and Perspectives of a Classic Treatment Strategy.Life (Basel, Switzerland) · 2024Review
- The histamine H3 receptor modulates dopamine D2 receptor-dependent signaling pathways and mouse behaviors.The Journal of biological chemistry · 2023Article
- Loss of apical sodium bile acid transporter alters bile acid circulation and reduces biliary damage in cholangitis.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Review
- Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis.Open medicine (Warsaw, Poland) · 2022Review
- Role of Immune Cells in Biliary Repair.Frontiers in immunology · 2022Review
- Exploring the role of mast cells in the progression of liver disease.Frontiers in physiology · 2022Review
- Feedback Signaling between Cholangiopathies, Ductular Reaction, and Non-Alcoholic Fatty Liver Disease.Cells · 2021Review
- Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?Cells · 2021Review
- Association between anti-acid therapies and advanced fibrosis in type 2 diabetics with biopsy-proven non-alcoholic fatty liver disease.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2020Article
- The Dynamic Interplay Between Mast Cells, Aging/Cellular Senescence, and Liver Disease.Gene expression · 2020Review
- Tryptophan Metabolism via the Kynurenine Pathway: Implications for Graft Optimization during Machine Perfusion.Journal of clinical medicine · 2020Article
- Biliary damage and liver fibrosis are ameliorated in a novel mouse model lacking l-histidine decarboxylase/histamine signaling.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Amelioration of Large Bile Duct Damage by Histamine-2 Receptor Vivo-Morpholino Treatment.The American journal of pathology · 2020Article
- Kaposi's Sarcoma-Associated Herpesvirus Infection Induces the Expression of Neuroendocrine Genes in Endothelial Cells.Journal of virology · 2020Article
- Inflammation and the Gut-Liver Axis in the Pathophysiology of Cholangiopathies.International journal of molecular sciences · 2018Review
- Blocking H1/H2 histamine receptors inhibits damage/fibrosis in Mdr2Hepatology (Baltimore, Md.) · 2018Article
- Mechanisms of cholangiocyte responses to injury.Biochimica et biophysica acta. Molecular basis of disease · 2018Review
- Knockout of l-Histidine Decarboxylase Prevents Cholangiocyte Damage and Hepatic Fibrosis in Mice Subjected to High-Fat Diet Feeding via Disrupted Histamine/Leptin Signaling.The American journal of pathology · 2018Article
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1-H4HRs. H1HR acts by Gαq activating IP(3)/Ca(2+), whereas H2HR activates Gα(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCα and protein kinase A (PKA) phosphorylation; and (3) PKCα silencing on H1HR-stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCα phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCα siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts.
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