Regulated expression of the platelet-derived growth factor A chain gene in microvascular endothelial cells

N. F. Starksen, G. R. Harsh IV, V. C. Gibbs, L. T. Williams

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Platelet-derived growth factor (PDGF) is composed of homologous polypeptide chains, termed A and B, that are expressed as mitogenically active A-A, B-B, or A-B dimers. Previous work in our laboratory has demonstrated that PDGF B chain mRNA expression is stimulated in microvascular endothelial cells by phorbol esters (PMA), thrombin, and transforming growth factor-β (TGF-β) and blocked by agents that elevate cyclic AMP (cAMP). Here we report the first evidence that the expression of A chain mRNA is also regulated in these cells. PDGF A chain mRNA levels were increased 5-25-fold by phorbol esters, thrombin, and TGF-β. Transcripts of four different sizes were induced. The increase in A chain mRNA stimulated by TGF-β was more prolonged (peak 4 h, duration 48 h) than the increase stimulated by PMA and thrombin (peak 4 h, duration 8 h). Among the agents known to increase B chain mRNA levels, PMA was most efficacious, followed in decreasing order by thrombin and TGF-β. However, for A chain mRNA induction by these same agents, the order was reversed; TGF-β was most efficacious, followed in decreasing order by thrombin and PMA. Agents that elevate cyclic AMP, known to block induction of B chain mRNA, blocked A chain induction by thrombin but had less effect on A chain mRNA induced by TGF-β. Thus PDGF A chain mRNA levels are regulated by the same agents that regulate B chain mRNA levels in microvascular endothelial cells. While the changes in A chain mRNA are qualitatively similar to the changes in B chain mRNA in microvascular endothelial cells, there are differences in the relative efficacies of these agents in the regulation of PDGF A and B chain genes. These differences suggest that the forms of PDGF produced by endothelial cells depend on the nature of the inducing stimulus.

Original languageEnglish (US)
Pages (from-to)14381-14384
Number of pages4
JournalJournal of Biological Chemistry
Volume262
Issue number30
StatePublished - 1987
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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