BACKGROUND & AIMS: The accelerated course of hepatic fibrosis that occurs in some patients after liver transplantation is a major clinical problem. This response may be caused by the antirejection therapeutics, and in an earlier report we showed that FK-506 enhanced the fibrogenic process in in vivo and in vitro models of liver fibrosis. In the present study, the aim was to determine whether a new immunosuppressive agent, rapamycin, enhances or inhibits liver fibrosis. METHODS: Effects of rapamycin were investigated in a carbon tetrachloride model of hepatic fibrosis in rats and on hepatic stellate proliferation in vitro. RESULTS: Rapamycin inhibited extracellular matrix deposition in the rat model of fibrogenesis as determined by histological analysis, collagen content, messenger RNA levels of procollagen and transforming growth factor beta1, and tissue transglutaminase activity. Moreover, rapamycin decreased platelet growth factor-induced proliferation of hepatic stellate cells. CONCLUSIONS: These findings indicate that the new antirejection agent rapamycin inhibits hepatic fibrosis and thus may become a valuable addition to the immunosuppression armamentarium.
BACKGROUND & AIMS: The accelerated course of hepatic fibrosis that occurs in some patients after liver transplantation is a major clinical problem. This response may be caused by the antirejection therapeutics, and in an earlier report we showed that FK-506 enhanced the fibrogenic process in in vivo and in vitro models of liver fibrosis. In the present study, the aim was to determine whether a new immunosuppressive agent, rapamycin, enhances or inhibits liver fibrosis. METHODS: Effects of rapamycin were investigated in a carbon tetrachloride model of hepatic fibrosis in rats and on hepatic stellate proliferation in vitro. RESULTS:Rapamycin inhibited extracellular matrix deposition in the rat model of fibrogenesis as determined by histological analysis, collagen content, messenger RNA levels of procollagen and transforming growth factor beta1, and tissue transglutaminase activity. Moreover, rapamycin decreased platelet growth factor-induced proliferation of hepatic stellate cells. CONCLUSIONS: These findings indicate that the new antirejection agent rapamycin inhibits hepatic fibrosis and thus may become a valuable addition to the immunosuppression armamentarium.
Authors: Liliana Schaefer; Wasiliki Tsalastra; Andrea Babelova; Martina Baliova; Jens Minnerup; Lydia Sorokin; Hermann-Josef Gröne; Dieter P Reinhardt; Josef Pfeilschifter; Renato V Iozzo; Roland M Schaefer Journal: Am J Pathol Date: 2007-01 Impact factor: 4.307
Authors: Cindy X Cai; Hema Buddha; Shobha Castelino-Prabhu; Zhiwei Zhang; Robert S Britton; Bruce R Bacon; Brent A Neuschwander-Tetri Journal: Dig Dis Sci Date: 2017-02-13 Impact factor: 3.199
Authors: Tien-I Karleen Su; Dinesh Khanna; Daniel E Furst; Gabriel Danovitch; Christina Burger; Paul Maranian; Philip J Clements Journal: Arthritis Rheum Date: 2009-12
Authors: Shailesh Agarwal; David Cholok; Shawn Loder; John Li; Christopher Breuler; Michael T Chung; Hsiao Hsin Sung; Kavitha Ranganathan; Joe Habbouche; James Drake; Joshua Peterson; Caitlin Priest; Shuli Li; Yuji Mishina; Benjamin Levi Journal: JCI Insight Date: 2016-12-08