REGULATION OF TRANSFORMING GROWTH-FACTOR EXPRESSION IN RAT INTESTINAL EPITHELIAL-CELL LINES

Autocrine and paracrine modulation of transforming growth factor expression was assessed in rat intestinal epithelial cell lines designated IEC-6 and IEC-17. Addition of the transforming growth factor-alpha (TGF-alpha) homologue epidermal growth factor (EGF) to media of subconfluent IEC-6 cells led to autocrine stimulation of TGF-alpha expression as well as increased expression of the transforming growth factor-beta-1 (TGF-beta-1). Increased expression of TGF-alpha was maximal between 3 and 6 h after addition of EGF and subsequently declined coincident with increasing level of expression of TGF-beta-1, which achieved maximal levels 6 h after addition of EGF and was sustained for more than 12 h. Addition of TGF-beta-1 also led to autocrine induction of its own expression coincident with suppression of TGF-alpha expresion. Addition of TGF-beta-1 was associated with increased expression of beta-actin when standardized to a constitutive transcript (GAPDH). Similar responses to addition of EGF and TGF-beta-1, were observed in another intestinal epithelial cell line, designated IEC-17. Modulation of expression of TGFs was attenuated when cells were grown on the complex extracellular matrix produced by the Engelbreth-Holm-Swarm tumor (Matrigel), reflecting the baseline induction of TGF-beta-1 expression when compared to IEC-6 and IEC-17 cells maintained on plastic. These observations suggest that expression of TGFs is controlled by autocrine mechanisms in intestinal epithelial cell lines and proliferation stimulated by TGF-alpha may be initially self-reinforcing but ultimately downregulated by induction of TGF-beta-1.