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Characterization of platelet-derived growth factor-induced p38 mitogen-activated protein kinase activation in

H Yamaguchi1, M Igarashi, A Hirata

  • 1Third Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.

European Journal of Clinical Investigation
|July 28, 2001
PubMed
Abstract

Insights

Platelet-derived growth factors (PDGFs) activate the p38 MAP kinase pathway in vascular smooth muscle cells (VSMCs) via MKK 3/6, independent of the ERK pathway. This activation influences cyclooxygenase-2 (COX-2) levels, suggesting a role in vascular inflammation.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cardiovascular research

Background:

  • Mitogen-activated protein (MAP) kinase superfamily regulates cell functions.
  • Platelet-derived growth factor (PDGF)-BB promotes vascular smooth muscle cell (VSMC) proliferation via extracellular-regulated protein kinases (ERKs), contributing to cardiovascular diseases.
  • The role of other PDGF isoforms and MAP kinase pathways (JNK, p38) in VSMCs remains unclear.

Purpose of the Study:

  • To investigate the effect of PDGFs on p38 MAP kinase activation in cultured rat VSMCs.
  • To determine if PDGFs activate parallel signal transduction pathways beyond ERKs.

Main Methods:

  • Cultured rat VSMCs were stimulated with PDGFs.
  • Inhibitors SB-203580 (p38 inhibitor) and PD-98059 (ERK inhibitor) were used.
  • Immunoblot analysis assessed the expression of MAP kinases, MKKs, phosphorylated proteins, and COXs.

Main Results:

  • PDGFs dose-dependently activated p38 phosphorylation, specifically inhibited by SB-203580.
  • PDGFs activated MKK 3/MKK 6 phosphorylation, but not JNK or ERK.
  • PDGF stimulation enhanced COX-2 levels after 72 hours, which was reduced by SB-203580.

Conclusions:

  • PDGFs activate the p38 cascade through MKK 3/6, independently of the ERK cascade, in rat VSMCs.
  • PDGFs regulate COX-2 levels, indicating a role in vascular wall inflammatory processes.

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