{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T02:15:26Z","timestamp":1779243326397,"version":"3.51.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Following liver injury, mast cells (MCs) migrate into the liver and are activated in patients with cholestasis. Inhibition of MC mediators decreases ductular reaction (DR) and liver fibrosis. Transforming growth factor beta 1 (TGF\u2010\u03b21) contributes to fibrosis and promotes liver disease. Our aim was to demonstrate that reintroduction of MCs induces cholestatic injury through TGF\u2010\u03b21.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Wild\u2010type, <jats:italic toggle=\"yes\">KitW\u2010sh\n                                 <\/jats:italic> (MC\u2010deficient), and multidrug resistance transporter 2\/ABC transporter B family member 2 knockout mice lacking l\u2010histidine decarboxylase were injected with vehicle or PKH26\u2010tagged murine MCs pretreated with 0.01% dimethyl sulfoxide (DMSO) or the TGF\u2010\u03b21 receptor inhibitor (TGF\u2010\u03b2Ri), LY2109761 (10 \u03bcM) 3 days before sacrifice. Hepatic damage was assessed by hematoxylin and eosin (H&amp;E) and serum chemistry. Injected MCs were detected in liver, spleen, and lung by immunofluorescence (IF). DR was measured by cytokeratin 19 (CK\u201019) immunohistochemistry and F4\/80 staining coupled with real\u2010time quantitative PCR (qPCR) for interleukin (IL)\u20101\u03b2, IL\u201033, and F4\/80; biliary senescence was evaluated by IF or qPCR for p16, p18, and p21. Fibrosis was evaluated by sirius red\/fast green staining and IF for synaptophysin 9 (SYP\u20109), desmin, and alpha smooth muscle actin (\u03b1\u2010SMA). TGF\u2010\u03b21 secretion\/expression was measured by enzyme immunoassay and qPCR. Angiogenesis was detected by IF for von Willebrand factor and vascular endothelial growth factor C qPCR. <jats:italic toggle=\"yes\">In vitro,<\/jats:italic> MC\u2010TGF\u2010\u03b21 expression\/secretion were measured after TGF\u2010\u03b2Ri treatment; conditioned medium was collected. Cholangiocytes and hepatic stellate cells (HSCs) were treated with MC\u2010conditioned medium, and biliary proliferation\/senescence was measured by 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20105\u2010(3\u2010carboxymethoxyphenyl)\u20102\u2010(4\u2010sulfophenyl)\u20102<jats:italic toggle=\"yes\">H<\/jats:italic>\u2010tetrazolium and qPCR; HSC activation evaluated for \u03b1\u2010SMA, SYP\u20109, and collagen type\u20101a expression. MC injection recapitulates cholestatic liver injury characterized by increased DR, fibrosis\/TGF\u2010\u03b21 secretion, and angiogenesis. Injection of MC\u2010TGF\u2010\u03b2Ri reversed these parameters. <jats:italic toggle=\"yes\">In vitro,<\/jats:italic> MCs induce biliary proliferation\/senescence and HSC activation that was reversed with MCs lacking TGF\u2010\u03b21.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our study demonstrates that reintroduction of MCs mimics cholestatic liver injury and that MC\u2010derived TGF\u2010\u03b21 may be a target in chronic cholestatic liver disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31497","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T19:27:06Z","timestamp":1596742026000},"page":"2397-2410","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Mast Cells Induce Ductular Reaction Mimicking Liver Injury in Mice Through Mast Cell\u2013Derived Transforming Growth Factor Beta 1 Signaling: [RETRACTED]"],"prefix":"10.1097","volume":"73","author":[{"given":"Konstantina","family":"Kyritsi","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vik","family":"Meadows","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine Research,Indianapolis,IN"},{"name":"Richard L. 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