Platelet-derived growth factor-BB-induced suppression of smooth muscle cell differentiation

Circ Res. 1992 Dec;71(6):1525-32. doi: 10.1161/01.res.71.6.1525.

Abstract

Previously, we demonstrated that treatment of postconfluent quiescent rat aortic smooth muscle cells (SMCs) with platelet-derived growth factor (PDGF)-BB dramatically reduced smooth muscle (SM) alpha-actin synthesis. In the present studies, we focused on the expression of two other SM-specific proteins, SM myosin heavy chain (SM-MHC) and SM alpha-tropomyosin (SM-alpha TM), to determine whether the actions of PDGF-BB were specific to SM alpha-actin or represented a global ability of PDGF-BB to inhibit expression of cell-specific proteins characteristic of differentiated SMCs. SM-MHC and SM-alpha TM expression were assessed by one- or two-dimensional gel electrophoretic analysis of proteins from cells labeled with [35S]methionine, as well as by Northern analysis of mRNA levels. Synthesis of both SM-specific proteins was decreased by 50-70% in PDGF-BB--treated cells as compared with cells treated with PDGF vehicle. Treatment of cells with 10% fetal bovine serum, which produced a mitogenic effect equivalent to that of PDGF-BB, decreased SM-MHC synthesis by 40% but increased SM-alpha TM synthesis. SM-MHC and SM-alpha TM mRNA expression was decreased by 80% at 24 hours in PDGF-BB--treated postconfluent SMCs, whereas treatment with 10% fetal bovine serum did not decrease the expression of SM-alpha TM mRNA but did inhibit SM-MHC mRNA expression by 36%. Consistent with the absence of detectable PDGF alpha-receptors on these cells, PDGF-AA had no effect on either mitogenesis or expression of SM-MHC or SM-alpha TM.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta
  • Autoradiography
  • Blotting, Northern
  • Cell Differentiation*
  • Cells, Cultured
  • DNA / biosynthesis
  • Electrophoresis, Gel, Two-Dimensional
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects*
  • Myosins / analysis
  • Phenotype
  • Platelet-Derived Growth Factor / pharmacology*
  • RNA, Messenger / analysis
  • Rats
  • Tropomyosin / analysis

Substances

  • Platelet-Derived Growth Factor
  • RNA, Messenger
  • Tropomyosin
  • DNA
  • Myosins