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Platelet-derived growth factor BB-induced p38 mitogen-activated protein kinase activation causes cell growth, but not

H Yamaguchi1, M Igarashi, A Hirata

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

Endocrine Journal
|October 18, 2001
PubMed

Insights

Platelet-derived growth factor (PDGF)-BB activates p38 mitogen-activated protein (MAP) kinase, promoting vascular smooth muscle cell growth. This pathway may contribute to cardiovascular diseases like atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cell Biology
  • Signal Transduction

Background:

  • Vascular smooth muscle cells (VSMCs) play a critical role in cardiovascular health and disease.
  • Platelet-derived growth factor (PDGF)-BB is a key regulator of VSMC function.
  • The role of p38 mitogen-activated protein (MAP) kinase in PDGF-BB signaling in VSMCs requires further elucidation.

Purpose of the Study:

  • To investigate the regulation of p38 MAP kinase by PDGF-BB in rat VSMCs.
  • To determine the biological effects of PDGF-BB-induced p38 MAP kinase activation on VSMC proliferation and apoptosis.

Main Methods:

  • Primary rat VSMCs were isolated using the media explant technique.
  • Cells were stimulated with PDGF-BB and/or the p38 MAP kinase inhibitor SB-203580.
  • p38 MAP kinase phosphorylation was assessed by immunoblot analysis.
  • DNA synthesis and content were measured using [3H]-thymidine incorporation and Hoechst-33258 dye.
  • Apoptosis was evaluated using the TUNEL method.

Main Results:

  • PDGF-BB induced dose-dependent phosphorylation of p38 MAP kinase, which was inhibited by SB-203580.
  • PDGF-BB increased VSMC DNA synthesis and content, effects abolished by SB-203580.
  • PDGF-BB did not alter the total protein levels of p38 MAP kinase.
  • No significant apoptotic changes were observed in PDGF-BB-stimulated VSMCs, regardless of SB-203580 treatment.

Conclusions:

  • PDGF-BB activates p38 MAP kinase signaling in VSMCs, leading to increased cell proliferation.
  • This study provides a molecular mechanism linking p38 MAP kinase activation to VSMC growth.
  • The findings suggest a potential role for the PDGF-BB/p38 MAP kinase pathway in the pathogenesis of cardiovascular diseases such as atherosclerosis.

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