Temporal and spacial distribution of transforming growth factor (TGF)-beta1 and procollagen gene expressions were studied in carbon tetrachloride (CC14)-induced liver fibrosis and TGF-beta1 was also studied in Solt-Farber's hepatocarcinogenesis model in rats. The studies were designed to clarify the pathogenesis as well as the involvement of different cell types in liver fibrosis, and also the role of TGF-beta1 during the development of hepatocellular carcinomas. Our study on liver fibrosis suggests that TGF-beta1 derived from inflammatory cells may have enhanced the expression of the procollagen alpha1(l) gene as well as that of the TGF-beta1 gene itself in Desmin-positive perisinusoidal cells by paracrine mechanism. The simultaneous expression of TGF-beta1 and procollagen genes in mesenchymal cells (Desmin-positive perisinusoidal cells, fibroblasts and inflammatory cells) during the fibrotic process also suggests the possibility that TGF-beta1 may have an important role in the production of liver fibrosis. In the carcinogenesis study, non-parenchymal cells of the liver are the principal source of TGF-beta1 production. It is hypothesized that regulatory effects of TGF-beta1 on growth of preneoplastic or carcinoma cells in the liver are exerted via paracrine mechanism.
