Heparin binding epidermal growth factor-like growth factor is a transforming growth factor β-regulated gene in intestinal epithelial cells

Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an EGF-related peptide with prominent effects on cell growth and migration. We explored potentially unique characteristics of HB-EGF in the intestinal epithelial cell line RIE-1. HB-EGF stimulated [H-3]thymidine incorporation to a level equivalent to transforming growth factor alpha (TGF alpha). HB-EGF also rapidly activated MAPK and induced cyclin D1 in mid-G1 with kinetics similar to TGF alpha. Unlike TGF alpha, HB-EGF mRNA was induced within 1 h by a variety of stimuli, including TGF beta 1. Maximal induction by TGF beta (7-fold) occurred within 2 h of treatment. Actinomycin D decay curves showed that TGF beta l had no effect on HB-EGF mRNA half-life (T-1/2 20 min). Induction of HB-EGF by TGF beta 1 was not affected by pretreatment with the MEK inhibitor PD-98059 while inhibition of protein kinase C either partially (calphostin C) or completely (staurosporin) blocked induction. Our results suggest that major differences exist in the regulation of the closely related EGF family members TGF alpha and HB-EGF. TGF beta and HB-EGF, structurally unrelated peptides with potent effects on wound healing, may function coordinately to mediate responses to wounding or cell injury in the intestinal epithelium. (C) 1999 Academic Press.