REGULATION OF TGF-BETA GENE-EXPRESSION IN RAT-LIVER INTOXICATED WITH CARBON-TETRACHLORIDE

Transforming growth factor β (TGFβ) has been implicated as having a central role in the postinflammatory tissue regeneration and fibrosis. To test its potential involvement in events that follow hepatotoxin-mediated liver regeneration and fibrosis, we quantitated changes in the steady-state levels of TGFβ mRNA in parenchymal and nonparenchymal cells at various times after an acute treatment with CCl4, and also compared TGFβ gene expression in these two cell types from livers subjected to chronic CCl4 treatment. The parenchymal and nonparenchymal cells from normal liver contained undetectable amounts of TGFβ mRNA. In contrast, we could readily detect TGFβ specific transcripts in both the parenchymal and nonparenchymal cells after acute injury. Nonparenchymal cells from acutely injured liver contained fivefold greater amounts of TGFβ mRNA, which peaked at 48 h and declined thereafter. In chronically treated rat livers (1, 2, 3, and 7 wk after the initiation of CCl4 treatment), increased expression of TGFβ mRNA was found only in nonparenchymal cells obtained after 2-3 wk of treatment. Strikingly large elevations in the steady-state levels of β-actin mRNA in CCl4-treated liver were also observed, which may be related to the known regenerative processes associated with acute liver toxicity. Changing dynamics of TGFβ gene expression, therefore, appear to be an important attribute of regenerating liver after acute or chronic CCl4 toxicity.