Molecular Mechanism Of Vascular Smooth Muscle Cell Adhesion And Migration Regulated By The Interaction Of Integrin With OPN

The vascular smooth muscle cell (VSMC) adhesion and migration are the important pathological mechanisms of some vascular remodeling diseases, such as hypertension, atherosclerosis and restenosis of percutaneous transluminal coronary angioplasty (PTCA). Many growth factors and extracellular matrix (ECM) proteins, for example, osteopontin (OPN) and fibronectin (FN), are involved in the regulation of VSMC biological behaviors. As the receptors of ECM, integrins not only mediate the interaction of the cells and ECM, but transduce signals from both the outside and inside of the cells, so that they can regulate cell adhesion, migration, differentiation, proliferation and apoptosis. Therefore, to clarify the signal transduction pathways of integrin-ECM interaction and their effects on cell biological behaviors are helpful to comprehend the molecular mechanisms of those remodeling cardiovascular diseases.To investigate the role of the interaction of OPN and integrin in regulating the adhesion and migration of VSMCs, the eukaryotic expression vector, pEGFP-C3-β3 CD, harboring the cytoplasmic domain of humanβ3 integrin subunit cDNA was constructed, and peptide-747 and peptide-759 including the NXXY motif were synthesized. Thereafter, they were transfected into VSMCs, and VSMC adhesion and migration activities were detected. Furthermore, the effects of OPN-integrin interaction on Src, focal adhesion kinase (FAK) and integrin-linked kinase (ILK) were evaluated. Then the adhesion and migration of VSMCs and the relationship of the three signal molecules were tested after the cells were treated with Src specific inhibitor PP2 or transfected by the recombinants of FRNK (an endogenous inhibitor of FAK activation) or the vector expressing ILK antisense RNA. In RNA...