Despite extensive efforts, little progress has been made in identifying the factors that induce hepatic fibrosis. Transforming growth factor-beta (TGF-beta) has been shown to enhance collagen production, therefore its role in hepatic fibrosis was investigated. Treatment of cultured hepatic cells with TGF-beta 1 increased type I procollagen mRNA levels 13-fold due to post-transcriptional gene regulation. When two animal models of hepatic fibrosis, murine schistosomiasis and CCl4-treated rats, were examined, they both exhibited increased levels of TGF-beta 1 gene expression at times that somewhat preceded the increase in collagen synthesis. In contrast, in murine schistosomiasis, mRNA levels of tumor necrosis factor and interleukin-1 peaked early in the fibrogenic process. Immunohistochemical analysis showed TGF-beta 1 to be present in normal mouse liver and to be markedly increased in mice infected with schistosomiasis. TGF-beta 1 appeared in the hepatic parenchyma, primarily in hepatocytes. These findings strongly suggest a role for TGF-beta 1 in a pathophysiological state.
In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis.
M J Czaja, F R Weiner, K C Flanders, M A Giambrone, R Wind, L Biempica, M A Zern; In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis.. J Cell Biol 1 June 1989; 108 (6): 2477–2482. doi: https://doi.org/10.1083/jcb.108.6.2477
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