TRANSFORMING GROWTH FACTOR-BETA(1) GENE ACTIVATION AND GROWTH OF SMOOTH-MUSCLE FROM HYPERTENSIVE RATS

Cultured vascular smooth muscle cells derived from the spontaneously h ypertensive rat (SHR) are known to replicate more rapidly than cells f rom the normotensive Wistar-Kyoto (WKY) rat. In this study we compared the responses of vascular smooth muscle cells from the two strains to transforming growth factor-beta 1 (TGF-beta 1) and evaluated its pote ntial to account for the different growth properties of these cells in response to a number of vascular-derived growth factors. TGF-beta 1 p otentiated the proliferative effects of epidermal growth factor, basic fibroblast growth factor, or the different isoforms of platelet-deriv ed growth factor on vascular smooth muscle cells from SHR but inhibite d growth factor-stimulated proliferation of vascular smooth muscle cel ls from WKY rats. These differential effects of TGF-beta 1 on prolifer ation could not be attributed to alterations in the expression of the type I, II, or III TGF-beta receptors but appeared more related to the ability of cells to autoinduce the TGF-beta 1 gene. TGF-beta 1 caused a time-dependent increase in its own mRNA levels in vascular smooth m uscle cells of WKY rats but attenuated levels in vascular smooth muscl e cells of SHR. This effect was specific to TGF-beta 1 autoinduction s ince similar elevations in TGF-beta 1 mRNA levels were observed when v ascular smooth muscle cells from the two rat strains were exposed to p horbol myristate acetate, basic fibroblast growth factor, or platelet- derived growth factor-BB. These data suggest that the production of TG F-beta 1 may contribute to the different growth properties of vascular smooth muscle cells from SHR and WKY rats through alterations in TGF- beta 1 signaling systems.