Platelet-derived growth factor-BB induces matrix metalloproteinase-2 expression and rat vascular smooth muscle cell

Ying Cui1, Yin-Wei Sun, Hai-Shuang Lin

  • 1Department of Biochemistry and Molecular Biology, Dalian Medical University, Lvshun, Dalian, 116044, People's Republic of China.

Insights

Platelet-derived growth factor-BB (PDGF-BB) increases matrix metalloproteinase-2 (MMP-2) in vascular cells. This process involves Rho-associated protein kinase (ROCK) and specific kinases, offering insights into atherosclerosis mechanisms.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cell Biology
  • Atherosclerosis Research

Background:

  • Matrix metalloproteinases (MMPs) are crucial in cardiovascular disease pathogenesis.
  • MMP expression is modulated by growth factors, inflammatory markers, and cytokines.

Purpose of the Study:

  • To investigate the role of platelet-derived growth factor-BB (PDGF-BB) in regulating MMP-2 expression in vascular smooth muscle cells (VSMC).
  • To elucidate the signaling pathways, including Rho-associated protein kinase (ROCK) and mitogen-activated protein kinases (MAPKs), involved in PDGF-BB-induced MMP-2 expression.

Main Methods:

  • VSMC were treated with PDGF-BB to assess MMP-2 expression.
  • Inhibitors of Rho-associated protein kinase (ROCK) (Y-27632) and MAPKs (U0126, SB203580) were used.
  • Small interfering RNA (siRNA) technology was employed to suppress ROCK-1/2 expression.

Main Results:

  • PDGF-BB significantly increased MMP-2 expression in a dose- and time-dependent manner.
  • Inhibition or suppression of ROCK markedly reduced PDGF-BB-induced MMP-2 expression.
  • Inhibition of extracellular signal-regulated kinase (ERK) and p38 MAPK also attenuated MMP-2 induction, indicating their involvement.

Conclusions:

  • PDGF-BB signaling in VSMC induces MMP-2 expression through a pathway involving ERK and p38 MAPK phosphorylation.
  • ROCK plays a significant regulatory role in PDGF-BB-mediated MMP-2 induction.
  • These findings reveal a novel mechanism contributing to atherosclerosis development.

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