Platelet‐derived growth factor‐induced destabilization of smooth muscle alpha‐actin mRNA

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Abstract
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 postcon‐fluent 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‐acti 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.