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

BJ Holycross, RS Blank, MM Thompson… - Circulation …, 1992 - Am Heart Assoc
BJ Holycross, RS Blank, MM Thompson, MJ Peach, GK Owens
Circulation research, 1992Am Heart Assoc
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 …
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)
Am Heart Assoc