Transforming growth factor β1 is a powerful modulator of platelet‐derived growth factor action in vascular smooth muscle cells

Publisher Website
Google Scholar
Abstract
We have studied the effect of transforming growth factor β1 (TGF‐β1) on vascular smooth muscle cell (SMC) mitogenesis and expression of thrombospondin and other growth related genes. We found that TGF‐β1 treatment of vascular SMC induced a prolonged increase in steady‐state mRNA levels of thrombospondin as well as α1 (lV) collagen. The increase began at approximately 2 h, peaked by 24 h, and remained considerably elevated 48 h after growth factor addition. There was a corresponding increase in thrombospondin protein as well as increased expression of several other secreted polypeptides. The increase in thrombospondin contrasted sharply with that observed for platelet‐derived growth factor (PDGF) which induced a rapid and transient increase in thrombospondin mRNA level. Although TGF‐β1 was able to directly enhance expression of thrombospondin as well as the growth‐related genes c‐fos and c‐myc, and induced c‐fos expression with identical kinetics as PDGF, it was unable to elicit [3H]thymidine incorporation into DNA in three independent smooth muscle cell strains. However, TGF‐β1 was able to strongly increase the mitogenic response of SMC to PDGF. Addition of both TGF‐β1 and PDGF to SMC also caused a synergistic increase in the expression of thrombospondin as well as c‐myc. Interestingly, in one other smooth muscle cell strain, a weak and delayed mitogenic response to TGF‐β1 alone was observed. Our results strongly suggest that induction of throm‐bospondin expression by TGF‐β1 and by PDGF occurs by distinct mechanisms. In addition, that TGF‐β1 can enhance PDGF‐induced mitogenesis may be due to the ability of TGF‐β1 to directly induce the expression of thrombospondin, c‐fos, c‐myc, and the PDGF β‐receptor.