{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:13:34Z","timestamp":1792260814934,"version":"4.4.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":224,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK058614"],"award-info":[{"award-number":["DK058614"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK065096"],"award-info":[{"award-number":["DK065096"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:p>\n                    Connective tissue growth factor (CTGF) is a matricellular protein that mediates cell\u2010matrix interaction through various subtypes of integrin receptors. This study investigated the role of CTGF and integrin \u03b1v\u03b26 in hepatic progenitor\/oval cell activation, which often occurs in the form of ductular reactions (DRs) when hepatocyte proliferation is inhibited during severe liver injury. CTGF and integrin \u03b1v\u03b26 proteins were highly expressed in DRs of human cirrhotic livers and cholangiocarcinoma. Confocal microscopy analysis of livers from\n                    <jats:italic toggle=\"yes\">Ctgf<\/jats:italic>\n                    promoter\u2010driven green fluorescent protein reporter mice suggested that oval cells and cholangiocytes were the main sources of CTGF and integrin \u03b1v\u03b26 during liver injury induced by 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine (DDC). Deletion of exon 4 of the\n                    <jats:italic toggle=\"yes\">Ctgf<\/jats:italic>\n                    gene using tamoxifen\u2010inducible Cre\u2010loxP system down\u2010regulated integrin \u03b1v\u03b26 in DDC\u2010damaged livers of knockout mice.\n                    <jats:italic toggle=\"yes\">Ctgf<\/jats:italic>\n                    deficiency or inhibition of integrin \u03b1v\u03b26, by administrating the neutralizing antibody, 6.3G9 (10 mg\/kg body weight), caused low levels of epithelial cell adhesion molecule and cytokeratin 19 gene messenger RNAs. Also, there were smaller oval cell areas, fewer proliferating ductular epithelial cells, and lower cholestasis serum markers within 2 weeks after DDC treatment. Associated fibrosis was attenuated, as indicated by reduced expression of fibrosis\u2010related genes, smaller areas of alpha\u2010smooth muscle actin staining, and low collagen production based on hydroxyproline content and Sirius Red staining. Finally, integrin \u03b1v\u03b26 could bind to CTGF mediating oval cell adhesion to CTGF and fibronection substrata and promoting transforming growth factor (TGF)\u2010\u03b21 activation\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    .\n                    <jats:italic toggle=\"yes\">Conclusions<\/jats:italic>\n                    : CTGF and integrin \u03b1v\u03b26 regulate oval cell activation and fibrosis, probably through interacting with their common matrix and signal partners, fibronectin and TGF\u2010\u03b21. CTGF and integrin \u03b1v\u03b26 are potential therapeutic targets to control DRs and fibrosis in related liver disease. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2015;61:678\u2010691)\n                  <\/jats:p>","DOI":"10.1002\/hep.27425","type":"journal-article","created":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T09:28:57Z","timestamp":1410254937000},"page":"678-691","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":75,"title":["Connective tissue growth factor and integrin \u03b1v\u03b26: A new pair of regulators critical for ductular reaction and biliary fibrosis in mice"],"prefix":"10.1097","volume":"61","author":[{"given":"Liya","family":"Pi","sequence":"first","affiliation":[{"name":"Departments of Pediatrics,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulette M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marda","family":"Jorgensen","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seh\u2010Hoon","family":"Oh","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H.","family":"Weinreb","sequence":"additional","affiliation":[{"name":"Biogen Idec, Inc.,Cambridge,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thu Le","family":"Trinh","sequence":"additional","affiliation":[{"name":"Pathology,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Protopapadakis","family":"Yianni","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Pathology,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Leask","sequence":"additional","affiliation":[{"name":"Schulich School of Medicine and Dentistry,University of Western Ontario,London,Ontario,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelia M.","family":"Violette","sequence":"additional","affiliation":[{"name":"Biogen Idec, Inc.,Cambridge,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward W.","family":"Scott","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Microbiology,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryon E.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics,University of Florida,Gainesville,FL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,1,20]]},"reference":[{"key":"hep27425-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1053\/j.gastro.2013.11.034","article-title":"Links between hepatic fibrosis, ductular reaction, and progenitor cell 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