{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:29:16Z","timestamp":1790303356322,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"funder":[{"name":"Biogen Idec, Inc."},{"name":"Stomedix, Inc."},{"name":"Department of Medicine (BIDMC)"},{"name":"Yat-sen University (Guangzhou, China)"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81301842"],"award-info":[{"award-number":["81301842"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Pearl River S&T Nova Program","award":["2014J2200087"],"award-info":[{"award-number":["2014J2200087"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>\n                    Integrin \u03b1v\u03b26 is rapidly up\u2010regulated on cells of epithelial lineage during tissue injury, where one of its primary functions is activation of latent transforming growth factor beta 1 (TGF\u03b21). In human liver cirrhosis, \u03b1v\u03b26 is overexpressed by cells comprising the ductular reaction, and its inhibition suppresses experimental biliary fibrosis in rodents. Here, we show that \u03b1v\u03b26 is expressed on the actively proliferating subset of hepatic progenitor cells and is required for their progenitor function\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    through integrin \u03b1v\u03b26\u2010dependent TGF\u03b21 activation. Freshly isolated \u03b1v\u03b26\n                    <jats:sup>+<\/jats:sup>\n                    liver cells demonstrate clonogenic potential and differentiate into cholangiocytes and functional hepatocytes\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    , whereas colony formation by epithelial cell adhesion molecule\u2010positive progenitor cells is blocked by \u03b1v\u03b26\u2010neutralizing antibody and in integrin beta 6\u2010deficient cells. Inhibition of progenitors by anti\u2010\u03b1v\u03b26 antibody is recapitulated by TGF\u03b21 neutralization and rescued by addition of bioactive TGF\u03b21. Genetic disruption or selective targeting of \u03b1v\u03b26 with 3G9 antibody potently inhibits progenitor cell responses in mouse models of chronic biliary injury and protects from liver fibrosis and tumorigenesis, two conditions clinically associated with exacerbated ductular reaction.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    These results suggest that \u03b1v\u03b26 is a promising target for chronic fibrotic liver diseases and associated cancers. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2016;63:217\u2013232)\n                  <\/jats:p>","DOI":"10.1002\/hep.28274","type":"journal-article","created":{"date-parts":[[2015,10,8]],"date-time":"2015-10-08T04:50:37Z","timestamp":1444279837000},"page":"217-232","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":113,"title":["Integrin \u03b1v\u03b26 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis"],"prefix":"10.1097","volume":"63","author":[{"given":"Zhen\u2010Wei","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Oncology,The First Affiliated Hospital of Sun Yat\u2010sen University,Guangzhou,China"},{"name":"Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center,Harvard Medical 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