| First Author | Sajid M | Year | 2003 |
| Journal | Am J Physiol Cell Physiol | Volume | 285 |
| Issue | 5 | Pages | C1330-8 |
| PubMed ID | 12878490 | Mgi Jnum | J:175201 |
| Mgi Id | MGI:5284809 | Doi | 10.1152/ajpcell.00475.2002 |
| Citation | Sajid M, et al. (2003) Alphavbeta3-integrin antagonists inhibit thrombin-induced proliferation and focal adhesion formation in smooth muscle cells. Am J Physiol Cell Physiol 285(5):C1330-8 |
| abstractText | Alphavbeta3-integrin antagonists reduced neointimal formation following vascular injury in eight different animal models. Because alpha-thrombin contributes to neointimal formation, we examined the hypothesis that alphavbeta3-integrins influence alpha-thrombin-induced signaling. Cultured rat aortic smooth muscle cells (RASMC) expressed alphavbeta3-integrins as demonstrated by immunofluorescence microscopy and fluorescence-activated cell sorting analysis. Proliferative responses to alpha-thrombin were partially inhibited by anti-beta3-integrin monoclonal antibody F11 and by cyclic RGD peptides. Immunofluorescence microscopy showed that alpha-thrombin stimulated a rapid increase in the formation of focal adhesions as identified by vinculin staining and that this effect was partially inhibited by alphavbeta3 antagonists. Beta3-integrin staining was diffuse in quiescent RASMC and did not concentrate at sites of focal adhesions following thrombin treatment. Alpha-thrombin elicited a time-dependent increase in activation of c-Jun NH2-terminal kinase-1 (JNK1) and in tyrosine phosphorylation of focal adhesion kinase (FAK). Alphavbeta3-integrin antagonists partially inhibited increases in JNK1 activity but had no effect on FAK phosphorylation. In SMC isolated from beta3-integrin-deficient mice, focal adhesion formation was impaired in response to thrombin but not sphingosine-1-phosphate, a potent activator of Rho. In summary, alphavbeta3-integrins play an important role in alpha-thrombin-induced proliferation and focal adhesion formation in RASMC. |
