Transforming growth factor-beta 1 and type I procollagen transcripts during regeneration and early fibrosis of rat...

The temporal and cellular distribution of transforming growth factor (TGF)-beta 1 and procollagen alpha 1(I) transcripts were examined during regeneration and early fibrosis of rat liver using in situ hybridization and Northern blot analyses. Surgical two-thirds partial hepatectomy (mechanical partial hepatectomy (PH)) and carbon tetrachloride administration (chemical PH) were used to initiate liver regeneration and fibrosis, respectively. Enhancement of TGF-beta 1 gene expression appeared as early as 4 hours after mechanical PH and reached maximum at 12 hours, which preceded the peak of DNA synthesis. However, the peak of TGF-beta 1 expression after carbon tetrachloride administration was observed after 2 days. The increase in expression of the procollagen alpha 1 (I) gene followed that of TGF-beta 1 after both mechanical and chemical PH. Increases in TGF-beta 1 and procollagen alpha 1 (I) transcripts were observed primarily in periductal and periportal cells, as well as in endothelial cells of the portal and central veins after mechanical and chemical PH. In the centrilobular necrotic areas after chemical PH, TGF-beta 1 and procollagen alpha 1 (I) transcripts were observed first in inflammatory cells and then in desmin-positive perisinusoidal cells and resulted in the accumulation of connective tissues. These data suggest that TGF-beta 1 derived from inflammatory cells may have enhanced the expression of the procollagen alpha 1 (I) gene as well as that of the TGF-beta 1 gene itself in desmin-positive perisinusoidal cells by paracrine mechanisms. This sequence of events may represent the initial stages of liver fibrogenesis.