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

Bin Liu1, Latika Dhawan, Burns C Blaxall

  • 1Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. Bin_liu@urmc.rochester.edu

Molecular and Cellular Biochemistry
|July 8, 2010
PubMed

Insights

Platelet-derived growth factor (PDGF) and angiotensin II (Ang) enhance monocyte chemoattractant protein-1 (MCP-1) mRNA stability in smooth muscle cells. Distinct pathways converge on protein kinase C delta (PKCδ), revealing its novel role in this process.

Area of Science:

  • Vascular Biology
  • Molecular Signaling
  • Inflammation Research

Background:

  • Monocyte chemoattractant protein-1 (MCP-1) is a key inflammatory chemokine implicated in atherosclerosis and arterial injury.
  • Platelet-derived growth factor (PDGF) and angiotensin II (Ang) are known to increase MCP-1 mRNA levels in vascular smooth muscle cells, primarily via mRNA stabilization.

Purpose of the Study:

  • To elucidate the specific intracellular signaling pathways by which PDGF and Ang stabilize MCP-1 mRNA in vascular smooth muscle cells.
  • To determine if these pathways involve receptor transactivation or converge on common downstream effectors.

Main Methods:

  • Investigated the roles of PDGF receptor beta and angiotensin II receptor AT1R in mediating MCP-1 mRNA stabilization.
  • Utilized specific inhibitors for protein kinase C (PKC), phosphoinositol 3-kinase (PI3K), Src, and NADPH oxidase (NADPHox).
  • Employed small interfering RNA (siRNA) targeting PKCδ and protein kinase D (PKD) to assess their involvement.

Main Results:

  • PDGF-BB and Ang stabilization of MCP-1 mRNA involved distinct proximal signaling pathways.
  • PDGF-BB's effect was blocked by PKC inhibitors and siRNA for PKCδ and PKD.
  • Ang's effect was blocked by Src and PKC inhibitors, and siRNA for PKCδ, but not PI3K or NADPHox inhibitors.

Conclusions:

  • Both PDGF-BB and Ang signaling pathways converge on the activation of PKCδ to enhance MCP-1 mRNA stability.
  • This study identifies a novel role for PKCδ in regulating mRNA stability within smooth muscle cells.
  • Distinct upstream signaling cascades activated by PDGF and Ang converge on a common downstream mediator, PKCδ.

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