TREATMENT OF RAT HEPATOCYTES WITH TRANSFORMING-GROWTH-FACTOR-BETA(1) INCREASES THEIR MITOGENIC ACTIVITY FOR CULTURED FAT-STORING CELLS

Fat storing cells (FSC) are the main precursor cell type of liver extr acellular matrix synthesis. It is shown here that damage of PC in cult ure by short-term or permanent exposure to transforming growth factor (TGF)-beta(1) increases strongly the mitogenic activity of hepatocyte- conditioned medium for FSC reaching proliferative effects higher than those induced by 10% fetal calf serum. More than 60% of TGF-beta-induc ed hepatocyte-generated mitogenic activity for FSC was abolished by ne utralizing anti-TGF-alpha antibody and by 10 mu M tyrphostin 25, a sel ective TGF-alpha/EGF receptor tyrosine kinase inhibitor. Untreated and TGF-beta-pretreated PC cultures showed positive immunofluorescent sta ining for TGF-alpha. The results propose potentially a new profibrogen ic role of TGF-beta via apoptotic and secondary necrotic damage of PC.