Platelet-derived growth factor-induced destabilization of smooth muscle alpha-actin mRNA.
We have previously shown that treatment of postconfluent, quiescent rat vascular smooth muscle cells (SMC) with platelet-derived growth factor (PDGF) dramatically reduced smooth muscle (SM) alpha-actin synthesis and SM alpha-actin mRNA abundance, suggesting a role for this mitogen in the control of SMC differentiation. In the present studies, we explored the molecular mechanisms whereby PDGF decreases SM alpha-actin mRNA levels. Treatment of postconfluent SMC with both platelet PDGF and recombinant PDGF-BB resulted in a dramatic and concentration-dependent decrease in SM alpha-actin mRNA levels. We observed no differences in efficacy between platelet PDGF and PDGF-BB, indicating that the PDGF-A chain is not required for the effect. The rate of decrease in SM alpha-actin mRNA abundance in PDGF-treated SMC was greater than that observed in cells treated with the transcriptional inhibitor, actinomycin D, with or without PDGF, indicating that PDGF induced a transcriptionally dependent destabilization of the cytosolic SM alpha-actin mRNA pool. This effect appeared selective for SM alpha-actin, in that there was no evidence of a similar change in non-muscle (NM) beta-actin mRNA stability following PDGF treatment. Results of nuclear run-on analyses showed no differences in SM alpha-actin transcription between PDGF- and vehicle-treated SMC at either 4 or 24 hours following treatment, demonstrating that decreases in transcription of the SM alpha-actin gene did not contribute to PDGF-induced changes in SM alpha-actin mRNA abundance. Results of these studies support a possible role for PDGF in regulation of SMC differentiation via a post-transcriptional control mechanism.
Corjay
M H
MH
Department of Physiology, University of Virginia School of Medicine, Charlottesville 22908.
Blank
R S
RS
Owens
G K
GK
D000199:Actins / Q000235:genetics*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects
D000199:Actins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger