Effect of epidermal growth factor on collagen formation in liver-derived epithelial clone cells

Biochemical and morphological studies were made on the effect of epidermal growth factor (EGF), isolated from male mouse submandibular gland, on collagen formation in clone RLC-18(4) epithelial cells from rat liver. EGF did not affect the number of these cells. EGF in the range of 0.5-500 ng/ml caused a dose-dependent increase in the content of hydroxyproline. It also increased the content of acidic glycosaminoglycans (AGAG), which are thought to be closely related to the formation of collagen fibers, and increased the activity of glutamine glucose-6-phosphate aminotransferase, an enzyme for AGAG synthesis but not that of N-acetyl-beta-glucosaminidase, an enzyme for AGAG degradation. It has no significant effect on the protein content of the cells. Studies on the effect of actinomycin D indicated that EGF may enhance de novo synthesis of hydroxyproline in liver epithelial cells and also that of glutamine glucose-6-phosphate aminotransferase, thus increasing the AGAG content of the cells. Antibody to EGF largely blocked collagen formation in the cells, even in the absence of EGF, indicating that EGF or EGF-like substances in the serum may affect collagen formation. In rat liver fibroblasts, EGF had little effect on collagen formation. These results show that EGF may act as a regulatory factor in collagen formation in liver epithelial cells, but not liver mesenchymal cells, in vitro.