CELLULAR-DISTRIBUTION OF TRANSFORMING GROWTH FACTOR-BETA-1 AND PROCOLLAGEN TYPE-1, TYPE-III, TYPE-IV TRANSCRIPTS IN CARBON TETRACHLORIDE-INDUCED RAT-LIVER FIBROSIS

The cellular distribution and temporal expression of transcripts from transforming growth factor-β1 (TGF-β1) and procollagen α1(I), α1(III), and α1(IV) genes were studied in carbon tetrachloride (CCl4)-induced rat liver fibrosis by using in situ hybridization technique. During the fibrotic process, TGF-β1 and procollagen genes were similarly and predominantly expressed in Desmin-positive perisinusoidal cells (e.g., fat-storing cells and myofibroblasts) and fibroblasts and their expression continued to be higher than those observed in control rats. These transcripts were also observed in inflammatory cells mainly granulocytes and macrophage-like cells at the early stages of liver fibrosis. The production of extracellular matrix along small blood vessels and fibrous septa coincided with the expression of these genes. Expression of TGF-β1 and procollagen genes were not detected in hepatocytes throughout the experiment. No significant differences in cellular distribution or time course of gene expressions among procollagen α1(I), α1(III), and α1(IV) were observed. Desmin-positive perisinusoidal cells and fibroblasts appeared to play the principal role in synthesis of collagens in CCl4-induced hepatic fibrosis. The simultaneous expression of TGF-β1 and procollagen genes in mesenchymal cells, including Desmin-positive perisinusoidal cells, during hepatic fibrosis suggests the possibility that TGF-β1 may have an important role in the production of fibrosis.