Chronic mild hypoxia increases expression of laminins 111 and 411 and the laminin receptor α6β1 integrin at the blood-brain barrier.
Chronic mild hypoxia increases expression of laminins 111 and 411 and the laminin receptor α6β1 integrin at the blood-brain barrier.
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DOI：
10.1016/j.brainres.2018.07.012
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发表时间：
2018-12-01
期刊：
影响因子：
2.9
通讯作者：
Milner R
中科院分区：
文献类型：
--
作者：
Halder SK;Kant R;Milner R
层粘连蛋白家族糖蛋白是血管基板的主要成分，在促进内皮分化和血脑屏障（BBB）稳定性方面起着重要作用。慢性轻度缺氧（CMH），小鼠暴露于8%的氧气两周，诱导中枢神经系统（CNS）强烈的血管重塑反应，包括内皮细胞增殖、血管生成、动脉生成以及紧密连接蛋白的表达增加，表明血管完整性增强。由于以往的研究强调了层粘胶蛋白在促进血管分化和血脑屏障稳定性方面的重要作用，本研究的目的是确定CMH是否影响脑血管中层粘胶蛋白及其细胞表面受体的表达。我们的研究表明，在14天的CMH期间，脑血管中特异性层粘连蛋白亚基α 1和α4的表达强烈上调，分别对应于层粘连蛋白111和411的表达增加，而α2和α5的表达水平没有明显变化。这伴随着内皮层粘连蛋白受体α6β1整联素的显著上调，但其他层粘连蛋白受体α1β1整联素或糖酐没有改变。鉴于层粘连蛋白在促进血管分化和稳定方面的指导作用，这些数据提示层粘连蛋白-α6β1整合素轴的上调是轻度缺氧触发的导致血脑屏障稳定性增强的分子反应的一部分。
The laminin family of glycoproteins are major constituents of the basal lamina of blood vessels, and play a fundamental role in promoting endothelial differentiation and blood-brain barrier (BBB) stability. Chronic mild hypoxia (CMH), in which mice are exposed to 8% O2 for two weeks, induces a strong vascular remodeling response in the central nervous system (CNS) that includes endothelial proliferation, angiogenesis, arteriogenesis as well as increased expression of tight junction proteins, suggestive of enhanced vascular integrity. As previous studies highlight an important role for laminin in promoting vascular differentiation and BBB stability, the goal of this study was to determine if CMH influences the expression of the laminins and their cell surface receptors in cerebral blood vessels. Our studies revealed that over a 14 day period of CMH, blood vessels in the brain showed strong upregulation of the specific laminin subunits αl and α4, corresponding to increased expression of laminins 111 and 411 respectively, with no discernible changes in the expression levels of the α2 or α5 laminin subunits. This was accompanied by marked endothelial upregulation of the laminin receptor α6β1 integrin but no alterations in the other laminin receptors α1β1 integrin or dystroglycan. In light of the instructive role for laminins in promoting vascular differentiation and stability, these data suggest that upregulation of the laminin-α6β1 integrin axis is part of the molecular response triggered by mild hypoxia that leads to enhanced BBB stability.
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影响因子：
1.7
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