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Involvement of matrix metalloproteinase-9 in platelet-activating factor-induced angiogenesis

Hyun-Mi Ko1, Yeong-Min Park, Bongnam Jung

  • 1Department of Biological Sciences, The Institute of Basic Sciences, Chonnam National University, Kwangju, Republic of Korea.

FEBS Letters
|April 26, 2005
PubMed

Insights

Platelet-activating factor (PAF) drives angiogenesis by activating NF-kappaB, which increases matrix metalloproteinase-9 (MMP-9). Inhibiting MMP-9 or NF-kappaB blocks this PAF-induced angiogenesis, highlighting their key roles.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Platelet-activating factor (PAF) is known to promote angiogenesis.
  • This process involves the activation of NF-kappaB and the synthesis of angiogenic factors.

Purpose of the Study:

  • To investigate the role of matrix metalloproteinase-9 (MMP-9) in PAF-induced angiogenesis.
  • To elucidate the mechanism by which PAF stimulates MMP-9 expression and activity.

Main Methods:

  • Utilized ECV304 cells to assess mRNA expression, protein synthesis, and MMP-9 activity.
  • Employed reporter gene assays with MMP-9 promoter and NF-kappaB subunits (p65, p50).
  • Investigated the effects of inhibitors (WEB2107, MMP-9, and NF-kappaB inhibitors) in vitro and in vivo (mouse Matrigel implantation model).

Main Results:

  • PAF significantly increased MMP-9 mRNA, protein synthesis, and activity in ECV304 cells via NF-kappaB activation.
  • PAF elevated MMP-9 promoter activity, which was suppressed by WEB2107 and NF-kappaB inhibitors.
  • NF-kappaB subunits (p65/p50) transfection enhanced MMP-9 promoter activity and mRNA expression.
  • Inhibition of MMP-9 or NF-kappaB significantly reduced PAF-induced angiogenesis in vivo and endothelial cell sprouting in vitro.

Conclusions:

  • NF-kappaB-dependent MMP-9 plays a critical role in mediating Platelet-Activating Factor (PAF)-induced angiogenesis.
  • Targeting the NF-kappaB/MMP-9 pathway may offer therapeutic strategies for angiogenesis-related conditions.

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