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Cell proliferation and cell cycle distribution were analyzed by bromodeoxyuridine and flow cytometry, respectively. The expression of collagen I and \u03b1-smooth muscle actin (\u03b1-SMA) were determined by Western blot, immunohistochemical staining, and real-time RT-PCR. The expression of cyclin D<jats:sub>1<\/jats:sub>, cyclin E, and p27<jats:sup>kip1<\/jats:sup>and phosphorylation of MEK, ERK, Akt, and 70-kDa ribosomal S6 kinase (p70S6K) were detected by Western blot. AKF-PD significantly inhibited PDGF-BB-induced HSC proliferation and activation by attenuating the expression of collagen I and \u03b1-SMA, causing G0\/G1 phase cell cycle arrest, reducing expression of cyclin D<jats:sub>1<\/jats:sub>and cyclin E, and promoting expression of p27<jats:sup>kip1<\/jats:sup>. AKF-PD also downregulated PDGF-BB-induced MEK, ERK, Akt, and p70S6K phosphorylation in HSCs. In rat liver fibrosis, AKF-PD alleviated hepatic fibrosis by decreasing necroinflammatory score and semiquantitative score, and reducing expression of collagen I and \u03b1-SMA. AKF-PD attenuated the progression of hepatic fibrosis by suppressing HSCs proliferation and activation via the ERK\/MAPK and PI3K\/Akt signaling pathways. AKF-PD may be used as a potential novel therapeutic agent against liver fibrosis.<\/jats:p>","DOI":"10.1152\/ajpgi.00471.2012","type":"journal-article","created":{"date-parts":[[2013,12,13]],"date-time":"2013-12-13T05:04:27Z","timestamp":1386911067000},"page":"G253-G263","source":"Crossref","is-referenced-by-count":35,"title":["Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells"],"prefix":"10.1152","volume":"306","author":[{"given":"Yu","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, China;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huixiang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan, 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