ArticleHepatology (Baltimore, Md.)2016
Inhibition of mast cell-secreted histamine decreases biliary proliferation and fibrosis in primary sclerosing cholangitis Mdr2(-/-) 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 61 papers.
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Who cites it
61 citing papers in PubMed, 80 citations in OpenAlex.
- Electroacupuncture at LI11 and SP10 is associated with alleviation of acute urticaria-like reactions in passive cutaneous anaphylaxis: an exploratory analysis of complement-related proteins and multiscale omics.Frontiers in immunology · 2026Article
- INVA8001, a novel and highly selective chymase inhibitor, ameliorates liver inflammation, fibrosis, and hyperplasia in Mdr2 knockout mice.Frontiers in medicine · 2026Article
- Ranitidine attenuates myocardial fibrosis by suppressing histamine/H2 receptor signaling and FAK/Src activation.Frontiers in pharmacology · 2026Article
- Mast cell tryptase-PAR2 axis promotes ovarian fibrosis through RNF152-mediated stabilization of Bcl-xL.Journal of ovarian research · 2025Article
- Article
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
- TGF-β1 Induces Mucosal Mast Cell Genes and is Negatively Regulated by the IL-3/ERK1/2 Axis.Cell communication and signaling : CCS · 2025Article
- Metabolism of hepatic stellate cells in chronic liver diseases: emerging molecular and therapeutic interventions.Theranostics · 2025Review
- Dynamic crosstalk between HSCs and liver microenvironment: multicellular interactions in the regulation of liver fibrosis.Frontiers in cell and developmental biology · 2025Review
- Steroid responsiveness in alcohol-associated hepatitis is linked to glucocorticoid metabolism, mitochondrial repair, and heat shock proteins.Hepatology communications · 2024Article
- Combination of H1 and H2 Histamine Receptor Antagonists: Current Knowledge and Perspectives of a Classic Treatment Strategy.Life (Basel, Switzerland) · 2024Review
- Hepatic inflammatory responses in liver fibrosis.Nature reviews. Gastroenterology & hepatology · 2023Review
- The Role of Inflammation in Cholestatic Liver Injury.Journal of inflammation research · 2023Review
- 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
- Interplay between Mast Cells and Regulatory T Cells in Immune-Mediated Cholangiopathies.International journal of molecular sciences · 2022Review
- Immune cells in alcohol-related liver disease.Liver research (Beijing, China) · 2022Review
- Review
- Mast cells in liver disease progression: An update on current studies and implications.Hepatology (Baltimore, Md.) · 2022Review
- Exploring the role of mast cells in the progression of liver disease.Frontiers in physiology · 2022Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledHepatic fibrosis is marked by activation of hepatic stellate cells (HSCs). Cholestatic injury precedes liver fibrosis, and cholangiocytes interact with HSCs promoting fibrosis. Mast cells (MCs) infiltrate following liver injury and release histamine, increasing biliary proliferation. We evaluated if inhibition of MC-derived histamine decreases biliary proliferation and fibrosis. Wild-type and multidrug resistance 2 knockout mice (9-11 weeks) were treated with cromolyn sodium for 1 week to block MC-derived histamine. Biliary mass and proliferation were evaluated by immunohistochemistry for cytokeratin 19 and Ki-67. Bile flow, bicarbonate excretion, and total bile acids were measured in all mice. Fibrosis was evaluated by sirius red/fast green staining and by quantitative polymerase chain reaction for alpha-smooth muscle actin, fibronectin, collagen type 1a, and transforming growth factor-beta 1. HSC activation was evaluated by quantitative polymerase chain reaction in total liver and immunofluorescent staining in tissues for synaptophysin 9. Histamine serum secretion was measured by enzymatic immunoassay. Mouse liver and human liver samples from control or primary sclerosing cholangitis patients were evaluated for MC markers by quantitative polymerase chain reaction and immunohistochemistry. In vitro, cultured MCs were transfected with histidine decarboxylase short hairpin RNA to decrease histamine secretion and subsequently cocultured with cholangiocytes or HSCs prior to measuring fibrosis markers, proliferation, and transforming growth factor-beta 1 secretion. Treatment with cromolyn sodium decreased biliary proliferation, fibrosis, histamine secretion, and bile flow in multidrug resistance 2 knockout mice. Primary sclerosing cholangitis mice and patients have increased MCs. Knockdown of MC histidine decarboxylase decreased cholangiocyte and HSC proliferation/activation.
conclusionMCs are recruited to proliferating cholangiocytes and promote fibrosis. Inhibition of MC-derived histamine decreases fibrosis, and regulation of MC mediators may be therapeutic for primary sclerosing cholangitis. (Hepatology 2016;64:1202-1216).
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