{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T04:30:44Z","timestamp":1781065844244,"version":"3.54.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Bile ducts are heterogenous in structure and function, and primary sclerosing cholangitis (PSC) damages specific bile ducts leading to ductular reaction (DR), mast cell (MC) infiltration, increased histamine release, inflammation, and fibrosis. Bile duct ligation (BDL) induces large duct damage via cyclic adenosine monophosphate (cAMP)\/extracellular signal\u2010related protein kinase (ERK) signaling, and large cholangiocytes express H2 histamine receptor (H2HR). We evaluated how MCs interact with large cholangiocytes during cholestasis. Male wild\u2010type (WT) and MC\u2010deficient (<jats:italic toggle=\"yes\">Kit<\/jats:italic>\n                           <jats:sup>\n                              W\u2010sh\n                           <\/jats:sup>) mice 10\u201312\u2009weeks of age were subjected to BDL for 7\u2009days. Select <jats:italic toggle=\"yes\">Kit<\/jats:italic>\n                           <jats:sup>\n                              W\u2010sh\n                           <\/jats:sup> mice were injected with MCs pretreated with control or H2HR antagonist (ranitidine, 25\u2009\u03bcm, 48\u2009h) via tail vein injection. <jats:italic toggle=\"yes\">In vitro<\/jats:italic>, MC migration toward small mouse cholangiocytes (SMCCs) and large mouse cholangiocytes (LMCCs) treated with lipopolysaccharide or histamine (\u00b1ranitidine) was measured. LMCCs were stimulated with MC supernatants pretreated with control, \u03b1\u2010methyl\u2010dl\u2010histidine (to block histamine release), or ranitidine. Liver damage, large duct DR\/senescence, inflammation, fibrosis, and cAMP\/ERK immunoreactivity increased in BDL WT and <jats:italic toggle=\"yes\">Kit<\/jats:italic>\n                           <jats:sup>\n                              W\u2010sh\n                           <\/jats:sup>+MC mice but decreased in BDL <jats:italic toggle=\"yes\">Kit<\/jats:italic>\n                           <jats:sup>\n                              W\u2010sh\n                           <\/jats:sup> and <jats:italic toggle=\"yes\">Kit<\/jats:italic>\n                           <jats:sup>\n                              W\u2010sh\n                           <\/jats:sup>+MC\u2010H2HR mice. <jats:italic toggle=\"yes\">In vitro<\/jats:italic>, MCs migrate toward damaged LMCCs (but not SMCCs) blocked by inhibition of H2HR. Loss of MC histamine or MC\u2010H2HR decreases LMCC proliferation, senescence, H2HR, and cAMP\/ERK levels. Human PSC livers have increased MC number found near DR, senescent ducts, and H2HR\u2010positive ducts. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Infiltrating MCs preferentially interact with large ducts via H2HR signaling promoting biliary and liver damage. Mediation of MCs may be a therapeutic strategy for PSC.<\/jats:p>","DOI":"10.1002\/hep4.2026","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T05:55:32Z","timestamp":1657259732000},"page":"2715-2731","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Mast cells selectively target large cholangiocytes during biliary injury via H2HR\u2010mediated cAMP\/pERK1\/2 signaling"],"prefix":"10.1097","volume":"6","author":[{"given":"Tianhao","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vik","family":"Meadows","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debjyoti","family":"Kundu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Kyritsi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Owen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Ceci","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8570-2519","authenticated-orcid":false,"given":"Guido","family":"Carpino","sequence":"additional","affiliation":[{"name":"Department of Movement,Human and Health Sciences,University of Rome \u201cForo Italico\u201d,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Onori","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological,Forensic Medicine and Orthopedics Sciences,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Gaudio","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological,Forensic Medicine and Orthopedics Sciences,Sapienza University of Rome,Rome,Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Glaser","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology,Texas A&M University,Bryan,Texas,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0741-8007","authenticated-orcid":false,"given":"Burcin","family":"Ekser","sequence":"additional","affiliation":[{"name":"Division of Transplant Surgery,Department of Surgery,Indiana University School of Medicine,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6658-3021","authenticated-orcid":false,"given":"Gianfranco","family":"Alpini","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,Indiana,USA"},{"name":"Richard L. 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