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The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP\u2013470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2013 and dimethylnitrosamine\u2013induced hepatic fibrosis were used for an<jats:italic toggle=\"yes\">in vivo<\/jats:italic>study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg\/kg body weight of TNP\u2013470. In CCl<jats:sub>4<\/jats:sub>\u2013induced fibrosis, factor VIII\u2013related antigen\u2013positive blood vessels, desmin\u2013, or \u03b1\u2013smooth muscle actin (\u03b1SMA)\u2013positive mesenchymal cells, bromodeoxyuridine (BrdU)\u2013positive mesenchymal cells also decreased in number by treatment with TNP\u2013470. In<jats:italic toggle=\"yes\">in vitro<\/jats:italic>experiments, a supplement of 1,000 ng\/mL TNP\u2013470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and\/or presence of platelet\u2013derived growth factor (PDGF). Expression of HSC activation markers,<jats:italic toggle=\"yes\">i.e.<\/jats:italic>, \u03b1SMA and PDGF receptor \u03b2, was also suppressed. The present results indicate that TNP\u2013470 inhibits HSC proliferation by blocking the cell\u2013cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect.<\/jats:p><\/jats:sec>","DOI":"10.1053\/jhep.2000.18658","type":"journal-article","created":{"date-parts":[[2003,6,21]],"date-time":"2003-06-21T14:16:51Z","timestamp":1056205011000},"page":"980-989","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":56,"title":["Inhibition of Hepatic Stellate Cell Proliferation and Activation by the Semisynthetic Analogue of Fumagillin Tnp\u2013470 in Rats"],"prefix":"10.1097","volume":"32","author":[{"given":"Yan Qing","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ikebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosei","family":"Hirakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Sowa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Nakatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norifumi","family":"Kawada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kaneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1053\/jhep.2000.18658-BIB1","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1172\/JCI115905","volume":"90","author":"Pinzani","year":"1991","journal-title":"J Clin Invest"},{"key":"10.1053\/jhep.2000.18658-BIB2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0074-7696(08)61977-4","volume":"66","author":"Wake","year":"1980","journal-title":"Int Rev Cytol"},{"key":"10.1053\/jhep.2000.18658-BIB3","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1056\/NEJM199304223281620","volume":"328","author":"Friedman","year":"1993","journal-title":"N Engl J Med"},{"key":"10.1053\/jhep.2000.18658-BIB4","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1172\/JCI114363","volume":"84","author":"Pinzani","year":"1989","journal-title":"J Clin Invest"},{"key":"10.1053\/jhep.2000.18658-BIB5","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/0270-9139(95)94092-8","volume":"22","author":"Gressner","year":"1995","journal-title":"J Hepatol"},{"key":"10.1053\/jhep.2000.18658-BIB6","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/978-4-431-67935-6_18","volume-title":"Liver Diseases and Hepatic Sinusoidal Cells","author":"Enzan","year":"1999","unstructured":", , , , , , et al. 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