Regulation of cell-matrix contacts and beta-catenin signaling in VSMC by integrin-linked kinase: implications for intimal thickening.

摘要: Vascular smooth muscle cell (VSMC) proliferation and migration is responsible for intimal thickening that occurs in restenosis atherosclerosis. Integrin-linked kinase (ILK) a serine/threonine protein implicated signaling pathways involved migration. We studied the involvement of ILK thickening. expression was significantly increased two models thickening: balloon-injured rat carotid arteries human saphenous vein organ cultures. Over-expression dominant negative (DN-ILK) reduced by approximately 50% cultures, demonstrating an important role activity on laminin up-regulated fibronectin, indicating modulated extracellular matrix composition. Inhibition siRNA knockdown DN-ILK decreased VSMC while wild type laminin, confirming essential both processes. Localization paxillin vinculin levels FAK phospho-FAK indicated inhibition focal adhesion formation. Additionally, attenuated presence cell–cell complex proteins N-cadherin β-catenin, β-catenin signaling. therefore suggest modulates at least part acting as molecular scaffold adhesions well modulating stability contact In summary, plays via regulation cell–matrix contacts