Adenosine monophosphate-activated protein kinase regulates platelet-derived growth factor-BB-induced vascular smooth...

Migration of vascular smooth muscle cells (VSMCs) is essential for repair of vascular injury, development of atherosclerotic lesions and restenosis after angioplasty or by-pass graft surgery. It has been reported that platelet-derived growth factor (PDGF)-BB induces VSMC migration via the p44/p42 mitogen-activated protein (MAP) kinase pathway and the phosphatidylinositol 3 (PI3)-kinase/Akt pathway. Adenosine monophosphate-activated protein kinase (AMPK) is generally known to regulate multiple metabolic pathway. In the present study, we investigated the involvement of AMPK in PDGF-BB-induced migration of VSMCs using, a VSMC line, A10 cells. PDGF-BB induced phosphorylation of AMPK-α at Thr-172 residue. Treatment of A10 cells with compound C, an AMPK inhibitor, suppressed PDGF-BB-induced migration in a concentration-dependent manner (0.01-1μM). Compound C truly attenuated PDGF-BB induced phosphorylation of acetyl-CoA carboxylase, a downstream substance of AMPK. Downregulation of AMPK-α expression by the siRNA appeared an anti-migratory effect on PDGF-BB-induced migration. PDGF-BB-induced phosphorylation of c-Raf, MEK1/2 or p44/p42 MAP kinase, and phosphorylation of PI3-kinase or Akt were markedly suppressed by compound C. In conclusion, our results strongly suggest that PDGF-BB induces activation of AMPK in VSMCs, and subsequently regulates the migration via both the p44/p42 MAP kinase pathway and the PI3-kinase/Akt pathway.