Transforming growth factor beta 1 is a powerful modulator of platelet-derived growth factor action in vascular smooth muscle cells

J Cell Physiol. 1992 Feb;150(2):232-42. doi: 10.1002/jcp.1041500203.

Abstract

We have studied the effect of transforming growth factor beta 1 (TGF-beta 1) on vascular smooth muscle cell (SMC) mitogenesis and expression of thrombospondin and other growth related genes. We found that TGF-beta 1 treatment of vascular SMC induced a prolonged increase in steady-state mRNA levels of thrombospondin as well as alpha 1 (IV) 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-beta 1 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-beta 1 was able to strongly increase the mitogenic response of SMC to PDGF. Addition of both TGF-beta 1 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-beta 1 alone was observed. Our results strongly suggest that induction of thrombospondin expression by TGF-beta 1 and by PDGF occurs by distinct mechanisms. In addition, that TGF-beta 1 can enhance PDGF-induced mitogenesis may be due to the ability of TGF-beta 1 to directly induce the expression of thrombospondin, c-fos, c-myc, and the PDGF beta-receptor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Collagen / genetics
  • Cycloheximide / pharmacology
  • Drug Synergism
  • Gene Expression / drug effects
  • Genes, fos
  • Genes, myc
  • In Vitro Techniques
  • Muscle, Smooth, Vascular / cytology*
  • Platelet Membrane Glycoproteins / genetics
  • Platelet-Derived Growth Factor / administration & dosage*
  • RNA, Messenger / genetics
  • Rabbits
  • Receptors, Cell Surface / genetics
  • Receptors, Platelet-Derived Growth Factor
  • Thrombospondins
  • Time Factors
  • Transforming Growth Factor beta / administration & dosage*

Substances

  • Platelet Membrane Glycoproteins
  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Receptors, Cell Surface
  • Thrombospondins
  • Transforming Growth Factor beta
  • Collagen
  • Cycloheximide
  • Receptors, Platelet-Derived Growth Factor