First Author | Song IS | Year | 2017 |
Journal | Sci Rep | Volume | 7 |
Issue | 1 | Pages | 11797 |
PubMed ID | 28924208 | Mgi Jnum | J:256549 |
Mgi Id | MGI:6109680 | Doi | 10.1038/s41598-017-12221-w |
Citation | Song IS, et al. (2017) Chebulinic acid inhibits smooth muscle cell migration by suppressing PDGF-Rbeta phosphorylation and inhibiting matrix metalloproteinase-2 expression. Sci Rep 7(1):11797 |
abstractText | Excessive migration of vascular smooth muscle cells (VSMCs) after vascular injury contributes to the development of occlusive vascular disease. Inhibition of VSMC migration is a validated therapeutic modality for occlusive vascular diseases, such as atherosclerosis and restenosis. We investigated the inhibitory effect of chebulinic acid (CBA) on cell migration and matrix metalloproteinase (MMP)-2 activation in platelet-derived growth factor (PDGF)-BB-induced mouse and human VSMCs. CBA significantly inhibited PDGF-BB-induced migration in mouse and human VSMCs, without inducing cell death. Additionally, CBA significantly blocked PDGF-BB-induced phosphorylation of the PDGF receptor (PDGF-R), Akt, and extracellular signal-regulated kinase (ERK)1/2 by inhibiting the activation of the PDGF-BB signalling pathway. In both mouse and human VSMCs, CBA inhibited PDGF-induced MMP-2 mRNA and protein expression as well as the proteolytic activity of MMP-2. Moreover, CBA suppressed sprout outgrowth formation of VSMCs from endothelium-removed aortic rings as well as neointima formation following rat carotid balloon injury. Taken together, our findings indicated that CBA inhibits VSMC migration by decreasing MMP-2 expression through PDGF-R and the ERK1/2 and Akt pathways. Our data may improve the understanding of the antiatherogenic effects of CBA in VSMCs. |