Effects of matrix metalloproteinase 13 on vascular smooth muscle cells migration via Akt-ERK dependent pathway.

Migration of vascular smooth muscle cells (VSMCs) is an early event of atherosclerosis, which is mediated mainly by matrix metalloproteinase (MMP) 2 and 9. Because MMP13 is associated with tumor cells migration, we hypothesized that MMP13 participates in VSMC migration induced by certain stimuli such as platelet-derived growth factor (PDGF) and angiotensin II (Ang II). We found that the mRNA level of MMP13 in rat aortic smooth muscle cells (RAoSMCs) was increased by both PDGF and Ang II. We observed the significant decrease of migration in PDGF- or Ang II-treated RAoSMCs by MMP13 specific inhibitor treatment. Silencing of MMP13 by a specific small interfering RNA (siRNA) significantly decreased expression of the active form of MMP13, which is followed by the decreased migration of PDGF- or Ang II-treated RAoSMCs. Interestingly, we observed synergistic inhibitory effects on migration by treatment with MMP2 and 13 or MMP9 and 13 inhibitors compared with that in single treatments. Moreover, we found that cordycepin, a known inhibitor of VSMC migration, caused significant downregulation of MMP2, 9, and 13 expression in PDGF-treated RAoSMCs. We further show that the expression level of MMP13 was significantly decreased by the treatment of Akt or ERK specific inhibitor in PDGF-treated RAoSMCs. Together, our data strongly suggest that MMP13 involves VSMCs migration via an Akt and ERK-dependent regulation [corrected].