Angiotensin II upregulates transforming growth factor-β type I receptor on rat vascular smooth muscle cells

Angiotensin II (Ang II) and transforming growth factor-β (TGF-β) modulate cell growth and metabolism. Our objective was to evaluate the effect of Ang II on the characteristics and expression of TGF-β receptors on vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats. The addition of TGF-β1 elicited a biphasic response on DNA synthesis in cultured VSMC in the absence of Ang II, but TGF-β1 did not stimulate DNA synthesis in the presence of Ang II. TGF-β binding data showed that Ang II increased the specific binding of 125I-TGF-β1 by enhancing the expression of lower affinity receptors and increasing the number of binding sites. Ang II alone did not stimulate DNA synthesis in these cultures. However, Ang II significantly stimulated DNA synthesis after the inhibition of endogenous TGF-β with a neutralizing antibody. The DNA synthesis stimulated by phorbol ester milisterol (PMA) was not affected by the TGF-β neutralizing antibody. Affinity labeling data revealed receptor-ligand complexes of 280, 85, and 70 kDa, corresponding to TGF-β type III, II, and I receptors, respectively. Incubation of VSMC with Ang II but not with PMA markedly increased the expression of the TGF-β type I receptor. Reverse transcription and polymerase chain reaction data also indicated that Ang II, but not PMA, significantly increased the expression of TGF-β type I receptor mRNA. Results suggest that Ang II increases the binding of TGF-β with upregulation of TGF-β type I receptor via a C-kinase–independent pathway. The enhanced expression of the TGF-β type I receptor may counteract Ang II-promoted growth of VSMC.