The effect of TGF-β receptor binding peptides on smooth muscle cells

TGF-β1 is a potent regulator of vascular smooth muscle cell (VSMC) proliferation, migration, and extracellular matrix (ECM) synthesis. In this study, we selected two peptides, IM-1 and IM-2, that bind to the TGF-β type II receptor (TGF-β RII) using phage display. IM-1 and IM-2 bind to the TGF-β RII, with a Kd of 1μM. Like TGF-β, IM-1 induced VSMC chemotaxis and PAI-1 mRNA expression, as determined using Boyden chambers and real time quantitative PCR. In contrast, IM-2 had no effect on VSMC chemotaxis or PAI-1 induction. Induction of ECM synthesis, involving proteins such as osteopontin and α-smooth muscle actin, was determined by ELISA. Osteopontin expression was inhibited by both peptides, but TGF-β-induced α-smooth muscle actin expression could only be inhibited by IM-1. In conclusion, IM-1 activity on VSMC is agonistic with TGF-β, except for ECM synthesis, whereas the IM-2 peptide is antagonistic for some examined TGF-β functions.