Smooth muscle cell matrix metalloproteinase production is stimulated via αvβ3 integrin
Smooth muscle cell matrix metalloproteinase production is stimulated via αvβ3 integrin
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DOI：
10.1161/01.atv.20.6.1467
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发表时间：
2000-06-01
影响因子：
8.7
通讯作者：
Giachelli, CM
中科院分区：
文献类型：
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作者：
Bendeck, MP;Irvin, C;Giachelli, CM
本研究验证了α（V）β（3）整合素受体在动脉损伤后平滑肌细胞（SMC）迁移中起关键作用并通过上调基质金属蛋白酶（MMP）活性促进迁移的假设。我们发现β 3整合素mRNA在球囊损伤大鼠颈动脉中被SMC上调，与MMP-1表达和早期SMC迁移一致。β 3整合素阻断抗体F11治疗显著降低了损伤后4天SMC向内膜的迁移，从对照组的110.8+/-30.8 cells/mm（2）降至F11治疗组的10.29+/-7.03 cells/mm（2）（P=0.008）。相比之下，在第4天对颈动脉中的中膜SMC增殖或中膜SMC数量没有影响。在体外实验中，我们发现人类新生的SMC产生MMP-1，但成人SMC没有。这可能是由于新生SMC表达α（V）β（3）整联蛋白受体，而成人SMC不表达。用骨桥蛋白刺激新生（α（V）β（3）+）SMC，骨桥蛋白是α（V）β（3）的基质配体，增加MMP-1的产生，从0 nmol/L骨桥蛋白的114.4+/-35.8 ng/lmL增加到100 nmol/L骨桥蛋白的232.5+/-57.5 ng/mL，最后，我们发现用血小板衍生生长因子-BE和骨桥蛋白共同刺激新生SMC增加了MMP-9的SMC产生。因此，我们的研究结果支持SMC α（V）β（3）整合素受体通过刺激SMC MMP的产生在调节迁移中起重要作用的假设。
This study tests the hypothesis that alpha(V)beta(3) integrin receptors play a critical role in smooth muscle cell (SMC) migration after arterial injury and facilitate migration through the upregulation of matrix metalloproteinase (MMP) activity. We showed that beta(3) integrin mRNA was upregulated by SMCs in the balloon-injured rat carotid artery in coincidence with MMP-1 expression and early SMC migration. Treatment with the beta(3) integrin-blocking antibody F11 significantly decreased SMC migration into the intima at 4 days after injury, from 110.8+/-30.8 cells/mm(2) in control rats to 10.29+/-7.03 cells/mm(2) in F11-treated rats (P=0.008). By contrast, there was no effect on medial SMC proliferation or on medial SMC number in the carotid artery at 4 days. In vitro, we found that human newborn SMCs produced MMP-1 but that adult SMCs did not. This was possibly due to the fact that newborn SMCs expressed alpha(V)beta(3) integrin receptors, whereas adult SMCs did not, Stimulation of newborn (alpha(V)beta(3)+) SMCs with osteopontin, a matrix ligand for alpha(V)beta(3), increased MMP-1 production from 114.4+/-35.8 ng/lmL at 0 nmol/L osteopontin to 232.5+/-57.5 ng/mL at 100 nmol/L osteopontin, Finally, we showed that stimulation of newborn SMCs with platelet-derived growth factor-BE and osteopontin together increased the SMC production of MMP-9. Thus, our results support the hypothesis that SMC alpha(V)beta(3) integrin receptors play an important role in regulating migration by stimulating SMC MMP production.