Increased expression of fibronectin and the α5β1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia
Increased expression of fibronectin and the α5β1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia
复制标题
DOI：
10.1016/j.mcn.2008.01.013
复制
发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
del Zoppo, Gregory J.
中科院分区：
文献类型：
--
作者：
Milner, Richard;Hung, Stephanie;del Zoppo, Gregory J.
细胞外基质（ECM）是血管生成和血管重塑的重要调节因子。我们以前的研究表明，在发育中的中枢神经系统血管生成毛细血管表达高水平的纤连蛋白及其受体α 5 β 1整合素，并且这种表达在发育过程中下调。由于脑缺氧导致血管生成反应，我们试图确定成人CNS中的血管生成血管是否重新表达纤连蛋白和α 5 β 1整合素。将10周龄小鼠进行0、4、7和14天的低压缺氧，并检测纤连蛋白/整合素表达。纤连蛋白和α 5整合素亚基在缺氧CNS中的毛细血管上强烈上调，在最早的时间点（4天）检查的效果最大。免疫荧光研究表明，α 5整合素表达的血管生成内皮细胞。鉴于纤连蛋白在其他系统中明确的血管生成作用，这项工作表明，纤连蛋白-α 5 β 1整合素表达的诱导可能是一个重要的分子开关，驱动缺氧CNS中的血管生成。(C)2008年爱思唯尔公司All rights reserved.
The extracellular matrix (ECM) is an important regulator of angiogenesis and vascular remodeling. We showed previously that angiogenic capillaries in the developing CNS express high levels of fibronectin and its receptor alpha 5 beta 1 integrin, and that this expression is developmentally downregulated. As cerebral hypoxia leads to an angiogenic response, we sought to determine whether angiogenic vessels in the adult CNS re-express fibronectin and the alpha 5 beta 1 integrin. Ten-week old mice were subject to hypobaric hypoxia for 0, 4, 7 and 14 days, and fibronectin/integrin expression examined. Fibronectin and the alpha 5 integrin subunit were strongly upregulated on capillaries in the hypoxic CNS, with the effect maximal at the earliest time point examined (4 days). Immunofluorescent studies demonstrated that the alpha 5 integrin was expressed by angiogenic endothelial cells. In light of the defined angiogenic role for fibronectin in other systems, this work suggests that induction of fibronectin-alpha 5 beta 1 integrin expression may be an important molecular switch driving angiogenesis in the hypoxic CNS. (C) 2008 Elsevier Inc. All rights reserved.