In vitro and in vivo association of transforming growth factor-β1 with hepatic fibrosis

Despite extensive efforts, little progress has been made in identifying the factors that induce hepatic fibrosis. Transforming growth factor-β (TGF-β) has been shown to enhance collagen production, therefore its role in hepatic fibrosis was investigated. Treatment of cultured hepatic cells with TGF-β1 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-β1 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-β1 to be present in normal mouse liver and to be markedly increased in mice infected with schistosomiasis. TGF-β1 appeared in the hepatic parenchyma, primarily in hepatocytes. These findings strongly suggest a role for TGF-β1 in a pathophysiological state.