Angiotensin II upregulates transforming growth factor-beta type I receptoron rat vascular smooth muscle cells

Angiotensin II (Ang II) and transforming growth factor-beta (TGF-beta) modu late cell growth and metabolism. Our objective was to evaluate the effect o f Ang II on the characteristics and expression of TGF-beta receptors on vas cular smooth muscle cells (VSMC) from Wistar-Kyoto rats. The addition of TG F-beta 1 elicited a biphasic response on DNA synthesis in cultured VSMC in the absence of Ang II, but TGF-beta 1 did not stimulate DNA synthesis in th e presence of Ang II. TGF-beta binding data showed that Ang II increased th e specific binding of I-125-TGF-beta 1 by enhancing the expression of lower affinity receptors and increasing the number of binding sites. Ang II alon e did not stimulate DNA synthesis in these cultures. However, Ang II signif icantly stimulated DNA synthesis after the inhibition of endogenous TGF-bet a with a neutralizing antibody. The DNA synthesis stimulated by phorbol est er milisterol (PMA) was not affected by the TGF-beta neutralizing antibody. Affinity labeling data revealed receptor-ligand complexes of 280, 85, and 70 kDa, corresponding to TGF-beta type III, II, and I receptors, respective ly. Incubation of VSMC with Ang II but not with PMA markedly increased the expression of the TGF-beta type I receptor. Reverse transcription and polym erase chain reaction data also indicated that Ang II, but not PMA, signific antly increased the expression of TGF-beta type I receptor mRNA. Results su ggest that Ang II increases the binding of TGF-beta with upregulation of TG F-beta type I receptor via a C-kinase-independent pathway. The enhanced exp ression of the TGF-beta type I receptor may counteract Ang II-promoted grow th of VSMC. (C) 2000 American Journal of Hypertension, Ltd.