Hyperbaric oxygen activates discoidin domain receptor 2 via tumour necrosis factor-α and the p38 MAPK pathway to increase vascular smooth muscle cell migration through matrix metalloproteinase 2

Kou-Gi Shyu, Bao Wei Wang, Hang Chang

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

DDR2 (discoidin domain receptor 2) regulates collagen turnover mediated by SMCs (smooth muscle cells) in atherosclerosis. HBO (hyperbaric oxygen) has been used in medical practice; however, the molecular mechanism of the beneficial effects of HBO is poorly understood. Furthermore, the effect of HBO on DDR2 has not been reported previously. In the present study, we investigated the cellular and molecular mechanisms of DDR2 regulation by HBO in VSMCs (vascular SMCs). Cells were exposed to 2.5 ATA (atmosphere absolute) of oxygen in a hyperbaric chamber. DDR2 protein (3.63-fold) and mRNA (2.34-fold) expression were significantly increased after exposure to 2.5 ATA HBO for 1 h. Addition of SB203580 and p38 MAPK (mitogen-activated protein kinase) siRNA (small interfering RNA) 30 min before HBO inhibited the induction of DDR2 protein. HBO also significantly increased DNA - protein binding activity of Myc/Max. Addition of SB203580 and an anti-TNF-α (tumour necrosis factor-α) monoclonal antibody 30 min before HBO abolished the DNA - protein binding activity induced by HBO. HBO significantly increased the secretion of TNF-α from cultured VSMCs. Exogenous addition of TNF-α significantly increased DDR2 protein expression, whereas anti-TNF-α and anti-(TNF-α receptor) antibodies blocked the induction of DDR2 protein expression. HBO significantly increased VSMC migration and proliferation, whereas DDR2 siRNA inhibited the migration induced by HBO. HBO increased activated MMP2 (matrix metalloproteinase 2) protein expression, and DDR2 siRNA abolished the induction of activated MMP2 expression induced by HBO. In conclusion, HBO activates DDR2 expression in cultured rat VSMCs. HBO-induced DDR2 is mediated by TNF-α and at least in part through the p38 MAPK and Myc pathways.

Original languageEnglish
Pages (from-to)575-583
Number of pages9
JournalClinical Science
Volume116
Issue number7
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Angiogenesis
  • Discoidin domain receptor 2 (DDR2)
  • Hyperbaric oxygen
  • Matrix metalloproteinase (MMP)
  • P38 mitogen-activated protein kinase (p38 MAPK)
  • Smooth muscle cell

ASJC Scopus subject areas

  • Medicine(all)

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