{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:43:58Z","timestamp":1784231038514,"version":"3.55.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":162,"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":[[2015,5]]},"abstract":"<jats:p>Liver fibrosis, a major cause of end\u2010stage liver diseases, is closely regulated by multiple growth factors and cytokines. The correlation of fibroblast growth factor 2 (FGF2) with chronic liver injury has been reported, but the exact functions of different FGF2 isoforms in liver fibrogenesis remain unclear. Here, we report on the differential expression patterns and functions of low\u2010 and high\u2010molecular\u2010weight FGF2 (namely, FGF2<jats:sup>lmw<\/jats:sup> and FGF2<jats:sup>hmw<\/jats:sup>, respectively) in hepatic fibrogenesis using a CCl<jats:sub>4<\/jats:sub>\u2010induced mouse liver fibrosis model. FGF2<jats:sup>hmw<\/jats:sup> displayed a robust increase in CCl<jats:sub>4<\/jats:sub>\u2010induced hepatic fibrosis and promoted fibrogenesis. In contrast, endogenous FGF2<jats:sup>lmw<\/jats:sup> exhibited a slight increase in hepatic fibrosis and suppressed this pathological progression. Moreover, exogenous administration of recombinant FGF2<jats:sup>lmw<\/jats:sup> potently ameliorated CCl<jats:sub>4<\/jats:sub>\u2010induced liver fibrosis. Mechanistically, we showed that FGF2<jats:sup>lmw<\/jats:sup> treatment attenuated hepatic stellate cell activation and fibrosis by epigenetic down\u2010regulation of Delta\u2010like 1 expression through the p38 mitogen\u2010activated protein kinase pathway. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: FGF2<jats:sup>lmw<\/jats:sup> and FGF2<jats:sup>hmw<\/jats:sup> have distinct roles in liver fibrogenesis. These findings demonstrate a potent antifibrotic effect of FGF2<jats:sup>lmw<\/jats:sup> administration, which may provide a novel approach to treat chronic liver diseases. (H<jats:sc>epatology<\/jats:sc> 2015;61:1708\u20131720)<\/jats:p>","DOI":"10.1002\/hep.27649","type":"journal-article","created":{"date-parts":[[2014,12,11]],"date-time":"2014-12-11T13:33:33Z","timestamp":1418304813000},"page":"1708-1720","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":41,"title":["Low\u2010molecular\u2010weight fibroblast growth factor 2 attenuates hepatic fibrosis by epigenetic down\u2010regulation of Delta\u2010like1"],"prefix":"10.1097","volume":"61","author":[{"given":"Ruo\u2010Lang","family":"Pan","sequence":"first","affiliation":[{"name":"College of Life Sciences,Zhejiang University,Hangzhou,China"},{"name":"Key Laboratory for Cell and Gene Engineering of Zhejiang Province,College of Life Sciences, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Xin","family":"Xiang","sequence":"additional","affiliation":[{"name":"College of Life Sciences,Zhejiang University,Hangzhou,China"},{"name":"Key Laboratory for Cell and Gene Engineering of Zhejiang Province,College of Life Sciences, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences,Zhejiang University,Hangzhou,China"},{"name":"Key Laboratory for Cell and Gene Engineering of Zhejiang Province,College of Life Sciences, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences,Zhejiang University,Hangzhou,China"},{"name":"Key Laboratory for Cell and Gene Engineering of Zhejiang Province,College of Life Sciences, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Nie","sequence":"additional","affiliation":[{"name":"College of Life Sciences,Zhejiang University,Hangzhou,China"},{"name":"Key Laboratory for Cell and Gene Engineering of Zhejiang Province,College of Life Sciences, Zhejiang University,Hangzhou,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendong","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Life Sciences,Zhejiang University,Hangzhou,China"},{"name":"Division of Molecular Diabetes Research, Department of Diabetes and Metabolic Diseases Research,Beckman Research Institute,City of Hope National Medical Center,Duarte,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Zhong","family":"Shao","sequence":"additional","affiliation":[{"name":"College of Life Sciences,Zhejiang University,Hangzhou,China"},{"name":"Key Laboratory for Cell and Gene Engineering of Zhejiang Province,College of Life Sciences, Zhejiang 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