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Platelet-derived growth factor and transforming growth factor-beta modulate the expression of matrix

I Ito1, E D Fixman, K Asai

  • 1Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC, Canada.

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
|June 16, 2009
PubMed
Abstract

Insights

Platelet-derived growth factor (PDGF) and TGF-beta influence matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) levels in airway smooth muscle cells, impacting cell migration and airway remodeling in asthma.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Respiratory Medicine

Background:

  • Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are implicated in asthma pathogenesis.
  • Their role in airway smooth muscle (ASM) cells may influence collagen turnover, cell migration, and airway remodeling.

Purpose of the Study:

  • To investigate the impact of TGF-beta and PDGF on MMP/TIMP expression in human ASM cells.
  • To determine the role of MMPs in ASM cell migration.

Main Methods:

  • Human ASM cells were stimulated with TGF-beta and/or PDGF.
  • MMP and TIMP expression and activity were assessed using RT-PCR, Western blot, and zymography.
  • ASM cell migration was evaluated using a Boyden-chamber assay.

Main Results:

  • PDGF significantly increased MMP-1 expression; PDGF plus TGF-beta synergistically increased MMP-3.
  • TIMP-1 was additively increased by TGF-beta and PDGF; MMP-2 and TIMP-2 were unaffected.
  • ERK and Smad pathway inhibitors modulated MMP and TIMP expression.
  • MMP-3 knockdown decreased ASM cell migration, while TIMP-1 suppression increased it.

Conclusions:

  • PDGF, with or without TGF-beta, may promote ASM cell migration by altering the MMP-TIMP balance via the ERK pathway.
  • This mechanism could contribute to airway remodeling in asthma.

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