Liver Cirrhosis Research Today is a free monthly online journal that collates and summarizes the latest research about Liver Cirrhosis, including details on alcohol, treatment, drugs, effects, causes. | ||||||||
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Imatinib mesylate (STI-571) attenuates liver fibrosis development in rats.Yoshiji H, Noguchi R, Kuriyama S, Ikenaka Y, Yoshii J, Yanase K, Namisaki T, Kitade M, Masaki T, Fukui H Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8521, Japan. yoshijih@naramed-u.ac.jp It is widely recognized that activated hepatic stellate cells (HSC) play a pivotal role in development of liver fibrosis. A platelet-derived growth factor (PDGF) is the most potent mitogen for HSC. The aim of this study was to examine the effect of imatinib mesylate (STI-571, Gleevec), a clinically used PDGF receptor (PDGFR) tyrosine kinase inhibitor, on development of experimental liver fibrosis. The rat model of pig serum-induced hepatic fibrosis was used to assess the effect of daily oral administration of STI-571 on the indexes of fibrosis. STI-571 markedly attenuated development of liver fibrosis and hepatic hydroxyproline and serum fibrosis markers. The number of alpha-smooth muscle actin-positive cells and mRNA expression of alpha2-(I)-procollagen, tissue inhibitor of metalloproteinases-1, and transforming growth factor-beta were also significantly suppressed by STI-571. Our in vitro study showed that STI-571 markedly attenuated PDGF-BB-induced proliferation and migration and alpha-SMA and alpha2-(I)-procollagen mRNA of activated HSC in a dose-dependent manner. STI-571 also significantly attenuated PDGF-BB-induced phosphorylation of PDGFR-beta, MEK1/2, and Akt in activated HSC. Because STI-571 is widely used in clinical practice, it may provide an effective new strategy for antifibrosis therapy. Published 13 April 2005 in Am J Physiol Gastrointest Liver Physiol, 288(5): G907-13.
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