Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA.
Exp Neurol. 2010 Jan;221(1):107-14. doi: 10.1016/j.expneurol.2009.10.007. Epub 2009 Oct 21.
beta1 integrin is a cell surface molecule that is critical for endothelial cell adhesion, migration and survival during angiogenesis. In the present study we employed in vivo and in vitro models to elucidate the role of beta1 integrin in vascular remodelling and stroke outcomes. At 24 h after cerebral ischemia and reperfusion (I/R), the ischemic cortex (ipsilateral area) exhibited modest beta1 integrin immunoreactivity and a robust increase was observed at 72 h. Double-label immunohistochemical analysis for beta1 integrin with neuronal (NeuN), microglial (Iba-1), astrocyte (GFAP), progenitor cell (Ng2) and blood vessel (collagen 4) markers showed that beta1 integrin expression only localized to blood vessels. In vitro studies using cultured endothelial cells and a beta1 integrin blocking antibody confirmed that beta1 integrin is required for endothelial cell migration, proliferation and blood vessel formation. In vivo studies in the cerebral I/R model using the beta1 integrin blocking antibody further confirmed that beta1 integrin signaling is involved in vascular formation and recovery following ischemic stroke. Finally, we found that beta1 integrin is critically involved in functional deficits and survival after a stroke. These results suggest that beta1 integrin plays important roles in neurovascular remodelling and functional outcomes following stroke, and that targeting the beta1 integrin signalling may provide a novel strategy for modulating angiogenesis in ischemic stroke and other pathological conditions.
β1 整合素是一种细胞表面分子，对于血管生成过程中内皮细胞的黏附、迁移和存活至关重要。在本研究中，我们采用体内和体外模型来阐明β1 整合素在血管重塑和中风结局中的作用。脑缺血再灌注（I/R）后 24 小时，缺血皮质（对侧区域）表现出适度的β1 整合素免疫反应，72 小时后观察到强烈的增加。β1 整合素与神经元（NeuN）、小胶质细胞（Iba-1）、星形胶质细胞（GFAP）、祖细胞（Ng2）和血管（胶原 4）标志物的双重免疫组织化学分析表明，β1 整合素表达仅局限于血管。体外培养的内皮细胞和β1 整合素阻断抗体的研究证实，β1 整合素是内皮细胞迁移、增殖和血管形成所必需的。在脑 I/R 模型中的体内研究进一步证实，β1 整合素信号参与缺血性中风后的血管形成和恢复。最后，我们发现β1 整合素在中风后的功能缺陷和存活中起着至关重要的作用。这些结果表明，β1 整合素在中风后的神经血管重塑和功能结局中发挥着重要作用，靶向β1 整合素信号可能为调节缺血性中风和其他病理状况中的血管生成提供一种新策略。
