Molecular and Cellular Biochemistry

, Volume 344, Issue 1–2, pp 73–79 | Cite as

Protein kinase Cδ mediates MCP-1 mRNA stabilization in vascular smooth muscle cells

  • Bin Liu
  • Latika Dhawan
  • Burns C. Blaxall
  • Mark B. Taubman
Article

Abstract

Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory chemokine that promotes atherosclerosis and is a mediator of the response to arterial injury. We previously demonstrated that platelet-derived growth factor (PDGF) and angiotensin II (Ang) induce the accumulation of MCP-1 mRNA in vascular smooth muscle cells mainly by increasing mRNA stability. In the present study, we have examined the signaling pathways involved in this stabilization of MCP-1 mRNA. The effect of PDGF (BB isoform) and Ang on MCP-1 mRNA stability was mediated by the PDGF β and angiotensin II receptor AT1R, respectively, and did not involve transactivation between the two receptors. The effect of PDGF-BB was blocked by inhibitors of protein kinase C (PKC), but not by inhibitors of phosphoinositol 3-kinase (PI3K), Src, or NADPH oxidase (NADPHox). In contrast, the effect of Ang was blocked by inhibitors of Src, and PKC, but not by inhibitors of PI3 K, or NADPHox. The effect of PDGF BB on MCP-1 mRNA stability was blocked by siRNA directed against PKCδ and protein kinase D (PKD), whereas the effect of Ang was blocked only by siRNA directed against PKCδ. These results suggest that the enhancement of MCP-1 mRNA stability by PDGF-BB and Ang are mediated by distinct “proximal” signaling pathways that converge on activation of PKCδ. This study identifies a novel role for PKCδ in mediating mRNA stability in smooth muscle cells.

Keywords

MCP-1 PDGF Angiotensin II Protein kinase C Atherosclerosis 

Notes

Acknowledgments

This study was supported by a grant from the National Institutes of Health Grant P01 HL77789 (MBT) and an American Heart Association Northeast Postdoctoral Fellowship (LD).

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Bin Liu
    • 1
  • Latika Dhawan
    • 1
  • Burns C. Blaxall
    • 1
  • Mark B. Taubman
    • 1
  1. 1.Department of Medicine, Aab Cardiovascular Research InstituteUniversity of Rochester Medical CenterRochesterUSA

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