Role of alpha5beta1 and alphavbeta3 integrins on smooth muscle cell spreading and migration in fibrin gels.
Role of alpha5beta1 and alphavbeta3 integrins on smooth muscle cell spreading and migration in fibrin gels.
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α5β1 和 αvβ3 整合素对纤维蛋白凝胶中平滑肌细胞铺展和迁移的作用。
DOI：
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发表时间：
2000
影响因子：
6.7
通讯作者：
S. Schwartz
中科院分区：
文献类型：
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作者：
Y. Ikari;K. Yee;S. Schwartz
纤维蛋白存在于血管损伤部位，是β 3整合素的主要基质配体之一。阻断平滑肌细胞上的β a3整合素被认为是防止再狭窄的潜在靶点，因为它可以抑制细胞附着和向纤维蛋白临时基质的迁移。人主动脉平滑肌细胞（HNB18E6E7）在24小时内稳定地在血浆凝胶中扩散。同时使用alpha5beta1和alphavbeta3整合素抗体可显著阻断细胞扩散（P <0.0001），但单独阻断任一整合素均不能抑制细胞扩散。GPenGRGDSPCA被认为是一种特异性的alphavbeta3拮抗剂，在500微米时抑制扩散，表明该肽阻断了alpha5beta1和alphavbeta3。同样，同时使用alpha5beta1和alphavbeta3抗体可以阻断向纤维蛋白凝胶的侵袭性迁移，但是单独阻断任一整合素都不能影响细胞迁移。另一个使用transwell的迁移试验显示了类似的结果。综上所述，alpha5beta1和alphavbeta3整合素都参与了平滑肌细胞向纤维蛋白凝胶的扩散和迁移。这些数据表明，单独阻断β a3整合素不会影响平滑肌细胞与纤维蛋白的相互作用。
Fibrin is found at sites of vascular injury and is one of the major matrix ligands for beta3 integrins. Blocking the beta3 integrin on smooth muscle cell is hypothesized as a potential target to prevent restenosis because it could inhibit cell attachment and migration into fibrin provisional matrix. Human aortic smooth muscle cells (HNB18E6E7) spread stably in plasma gels within 24 h. Cell spreading was dramatically blocked by simultaneous use of alpha5beta1 and alphavbeta3 integrin antibodies (P <0.0001), however, blocking of either integrin alone failed to inhibit spreading. GPenGRGDSPCA, which has been considered a specific alphavbeta3 antagonist, inhibited spreading at 500 microM, suggesting that the peptide blocked both alpha5beta1 and alphavbeta3. Similarly, invasive migration into fibrin gels was blocked by simultaneous use of both alpha5beta1 and alphavbeta3 antibodies, however, blocking of either integrin alone failed to effect cell migration. Another migration assay using transwell indicated similar results. In conclusion, both alpha5beta1 and alphavbeta3 integrins are responsible for smooth muscle cell spreading and migration into fibrin gels. These data suggest that blocking beta3 integrin alone would not affect smooth muscle cell interaction with fibrin.