Wingless/Wnt信号与缺血性脑中风中神经血管单元相关的研究进展

Wingless(Wnt)信号通路作为一个复杂的蛋白质作用网络,通过自分泌和旁分泌作用调节多种细胞的发生和发育,具有重要的生物学意义。近年来针对神经和血管的整体保护,提出了神经血管单元(neurovascular unit,NVU)的新模型,并发现Wnt信号通路在缺血性脑中风神经血管单元保护中可能发挥重要作用。Wnts家族与卷曲蛋白(Friz-zled)/低密度脂蛋白受体相关蛋白5/6(low-density lipopro-tein related proteins 5/6,LRP5/6)结合,进入细胞内,经过一系列反应,可激活核内缺氧诱导因子-1α(hypoxia induciblefactor-1α,HIF-1α),在基因水平上直接调控血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达(Wnt信号可作为HIF-1α和VEGF的上游信号),继而上调β-catenin信号分子,激活其下游信号分子从而调节血脑屏障(blood brain barrier,BBB)及NVU相关基因和蛋白的水平,即从整体上促进缺血性脑中风损伤后修复。

Advances in studies on correlations between Wingless/Wnt signals and the neurovascular unit in ischemic stroke

Wingless(Wnts) signaling pathway acts as a complex protein interaction network,through autocrine and paracrine to regulate the occurrence and development of a variety of cells,which has biological significance.In recent years,a new model,the neurovascular unit(NVU) aimed at the overall protection of nerves and blood vessels,has been put forward,and becomes a hot topic.Wnt signaling pathway may play an important role in neurovascular unit protection of ischemic stroke.Wnts family combining with Frizzled / Low-density Lipoprotein related proteins 5 /6 proteins(LRP5 /6),which transfer into cells,can activate hypoxia inducible factor-1α(HIF-1α) after a series of reactions,regulate the vascular endothelial growth factor(VEGF) expression at the gene level(Wnts is as upstream signal of HIF1α and VEGF),and then activate the down-stream signal molecules through up-regulating the β-catenin to regulate gene and protein level of the Blood Brain Barrier(BBB) and NVU as the final result,which promotes the repair after the ischemic stroke injury at the overall level.