EXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA IN REGENERATING LIVER AND DURING HEPATIC DIFFERENTIATION

Both the level of expression and cellular distribution of transcripts for transforming growth factor-alpha (TGF-alpha) were studied in adult rat liver after partial hepatectomy and during hepatic differentiation in fetal, neonatal, and adult livers by northern blot analysis and in situ hybridization. A marked increase in the expression of TGF-alpha was observed in neonatal livers and in adult livers after partial hepatectomy and during hepatic regeneration following modification of the Solt-Farber protocol. Quantitation of silver grains after in situ hybridization with a TGF-alpha riboprobe revealed a sixfold to eightfold increase in fetal and neonatal hepatocytes. Moreover, the expression of TGF-alpha in the liver 3 wk after birth was still fourfold higher than that of the adult quiescent liver. Both proliferating oval cells and basophilic foci of hepatocytes generated by modification of the Solt-Farber protocol were positive for TGF-alpha transcripts. The level of TGF-alpha transcripts was sixfold higher in the basophilic foci than in the surrounding liver. High concentrations of TGF-alpha transcripts were observed in the oval cells that lined pseudoducts and in the transitional cells proliferating within the ducts. The combination of in situ hybridization and immunocytochemistry using cell-specific antibodies revealed the presence of TGF-alpha transcripts in both oval cells and in perisinusoidal stellate cells. The observation that TGF-alpha transcripts were found both in primitive liver epithelial cells and perisinusoidal stellate cells suggests that this growth factor, in addition to its mitogenic action, may also have other important functions in the liver.