Differential regulation of transforming growth factor receptors by angiotensin II and transforming growth factor-β 1 in vascular smooth muscle

Publisher Website
Google Scholar
Abstract
Angiotensin II (Ang II) and transforming growth factor (TGF) β1 play a role in vascular remodeling in hypertension. In this process they may interact on various levels, including that of receptor regulation. This consideration prompted the present study on transcriptional regulation of TGF-β receptors by Ang II and TGF-β in vascular smooth muscle cells. Transcriptional expression of the components of the TGF-β system was demonstrated for TGF-β and for TGF-β receptors I, II, and III. As measured by quantitative reverse transcriptase polymerase chain reaction, TGF-β mRNA increased about 2.4-fold in the presence of 40 pM exogenous TGF-β. Ang II at 10–6 M increased TGF-β mRNA 2.5-fold compared to control cells (PPP<0.05). TGF-β effects were abrogated by coincubation with a TGF-β neutralizing antibody, and Ang II effects were abrogated by losartan, an AT-1 receptor antagonist. Coincubation of Ang II with the TGF-β neutralizing antibody did not inhibit the effect of Ang II, indicating that the short-term effects of Ang II on the expression of the TGF-β receptors are not mediated via TGF-β. Furthermore, Ang II stimulated DNA synthesis even in the presence of the TGF-β neutralizing antibody. In conclusion, this study indicates (a) that in vascular smooth muscle TGF-β receptors are regulated on the RNA level by TGF-β and Ang II, and (b) that Ang II dependent regulation of TGF-β receptors is at least partially independent of endogenous TGF-β. Stimulation of the transcriptional expression of TGF-β receptors by Ang II may increase sensitivity of vascular smooth muscle cells to TGF-β.

This publication has 0 references indexed in Scilit: