{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:30:47Z","timestamp":1792114247072,"version":"4.4.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"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":[[2021,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Nonalcoholic fatty liver disease (NAFLD) is simple steatosis but can develop into nonalcoholic steatohepatitis (NASH), characterized by liver inflammation, fibrosis, and microvesicular steatosis. Mast cells (MCs) infiltrate the liver during cholestasis and promote ductular reaction (DR), biliary senescence, and liver fibrosis. We aimed to determine the effects of MC depletion during NAFLD\/NASH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Wild\u2010type (WT) and <jats:italic toggle=\"yes\">KitW\u2010sh\n                                 <\/jats:italic> (MC\u2010deficient) mice were fed a control diet (CD) or a Western diet (WD) for 16\u00a0weeks; select WT and <jats:italic toggle=\"yes\">KitW\u2010sh\n                                 <\/jats:italic> WD mice received tail vein injections of MCs 2 times per week for 2\u00a0weeks prior to sacrifice. Human samples were collected from normal, NAFLD, or NASH mice. Cholangiocytes from WT WD mice and human NASH have increased insulin\u2010like growth factor 1 expression that promotes MC migration\/activation. Enhanced MC presence was noted in WT WD mice and human NASH, along with increased DR. WT WD mice had significantly increased steatosis, DR\/biliary senescence, inflammation, liver fibrosis, and angiogenesis compared to WT CD mice, which was significantly reduced in <jats:italic toggle=\"yes\">KitW\u2010sh\n                                 <\/jats:italic> WD mice. Loss of MCs prominently reduced microvesicular steatosis in zone 1 hepatocytes. MC injection promoted WD\u2010induced biliary and liver damage and specifically up\u2010regulated microvesicular steatosis in zone 1 hepatocytes. Aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) expression is reduced in WT WD mice and human NASH but increased in <jats:italic toggle=\"yes\">KitW\u2010sh\n                                 <\/jats:italic> WD mice. MicroRNA 144\u20103 prime (miR\u2010144\u20103p) expression was increased in WT WD mice and human NASH but reduced in <jats:italic toggle=\"yes\">KitW\u2010sh\n                                 <\/jats:italic> WD mice and was found to target ALDH1A3.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>MCs promote WD\u2010induced biliary and liver damage and may promote microvesicular steatosis development during NAFLD progression to NASH through miR\u2010144\u20103p\/ALDH1A3 signaling. Inhibition of MC activation may be a therapeutic option for NAFLD\/NASH treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31713","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T04:55:39Z","timestamp":1610686539000},"page":"164-182","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":50,"title":["Mast Cells Promote Nonalcoholic Fatty Liver Disease Phenotypes and Microvesicular Steatosis in Mice Fed a Western Diet"],"prefix":"10.1097","volume":"74","author":[{"given":"Lindsey","family":"Kennedy","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine,Indianapolis,IN"}],"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,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Sybenga","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology,Vanderbilt University School of Medicine,Nashville,TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Demieville","sequence":"additional","affiliation":[{"name":"Central Texas Veterans Health Care System,Texas A&M University College of Medicine,Bryan,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixian","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hargrove","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology,Texas A&M University College of Medicine,Bryan,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0741-8007","authenticated-orcid":false,"given":"Burcin","family":"Ekser","sequence":"additional","affiliation":[{"name":"Department of Transplant Surgery,Indiana University School of Medicine,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Dar","sequence":"additional","affiliation":[{"name":"Division of Immunology and Organ Transplantation,Department of Surgery,University of Texas Health Science Center at Houston,Houston,TX"}],"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,Indianapolis,IN"}],"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,Indianapolis,IN"}],"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,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linh","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine,Indianapolis,IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology,Texas A&M University College of Medicine,Bryan,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Glaser","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology,Texas A&M University College of Medicine,Bryan,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyin","family":"Meng","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of Medicine,Indianapolis,IN"},{"name":"Richard L. 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