{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T19:04:48Z","timestamp":1781723088930,"version":"3.54.5"},"reference-count":31,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p> Fibroblast growth factor 2 (FGF-2) and its main receptor FGFR1 have been shown to promote hepatic stellate cell (HSC) activation and proliferation. However, scant information is available on the anti-fibrogenic activity of FGFR1 inhibitors. The aim of this study was to assess the impact of a selective FGFR1 tyrosine kinase inhibitor NP603 on HSC proliferation and hepatic fibrosis. We demonstrated that rat primary HSCs secreted significant amounts of FGF-2, and its tyrosine phosphorylation of FGFR1 was attenuated by NP603. NP603 inhibited HSC activaton by measuring the expression of \u03b1-smooth muscle actin (\u03b1-SMA) and the production of type I collagen using ELISA. Furthermore, NP603 (25 \u03bcM) in vitro strongly suppressed HSC growth induced by FGF-2 (10 ng\/ml) and FCS. This effect correlated with the suppression of extracellular-regulated kinase (ERK) activity and its downstream targets cyclin D1 and p21. In addition, PO NP603 (20 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) administration significantly decreased hepatic collagen deposition and \u03b1-SMA expression in CCl<jats:sub>4<\/jats:sub>-treated rats. Collectively, these studies suggest that selective blocking of the FGFR1-mediated pathway could be a promising therapeutic approach for the treatment of hepatic fibrosis. <\/jats:p>","DOI":"10.1152\/ajpcell.00452.2010","type":"journal-article","created":{"date-parts":[[2011,5,5]],"date-time":"2011-05-05T01:00:32Z","timestamp":1304557232000},"page":"C469-C477","source":"Crossref","is-referenced-by-count":44,"title":["NP603, a novel and potent inhibitor of FGFR1 tyrosine kinase, inhibits hepatic stellate cell proliferation and ameliorates hepatic fibrosis in rats"],"prefix":"10.1152","volume":"301","author":[{"given":"Nan","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, GuangZhou;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, GuangZhou;"},{"name":"Department of Immunology, Anhui Medical University, HeFei; 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