Platelet-derived growth factor-BB-induced suppression of smooth muscle cell differentiation.
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)
Holycross
B J
BJ
Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville 22908.
Blank
R S
RS
Thompson
M M
MM
Peach
M J
MJ
Owens
G K
GK
D000818:Animals; D001011:Aorta; D001345:Autoradiography; D015152:Blotting, Northern; D002454:Cell Differentiation; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D015180:Electrophoresis, Gel, Two-Dimensional; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D009218:Myosins / Q000032:analysis; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014335:Tropomyosin / Q000032:analysis
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D014335:Tropomyosin; D004247:DNA; D009218:Myosins