X‐box binding protein l splicing attenuates brain microvascular endothelial cell damage induced by oxygen‐glucose deprivation through the activation of phosphoinositide 3-kinase/protein kinase B, extracellular signal-regulated kinases, and hypoxia-inducib
X‐box binding protein l splicing attenuates brain microvascular endothelial cell damage induced by oxygen‐glucose deprivation through the activation of phosphoinositide 3-kinase/protein kinase B, extracellular signal-regulated kinases, and hypoxia-inducib
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X-box 结合蛋白 l 剪接通过激活磷酸肌醇 3-激酶/蛋白激酶 B、细胞外信号调节激酶和缺氧诱导，减轻缺氧葡萄糖诱导的脑微血管内皮细胞损伤
DOI：
10.1002/jcp.27614
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发表时间：
2018
影响因子：
5.6
通讯作者：
Zhang Mengqi
中科院分区：
文献类型：
--
作者：
Shi Shupeng;Tang Mimi;Li Honglei;Ding Hui;Lu Yangfan;Gao Lijuan;Wu Qian;Zhou Luo;Fu Yujiao;Xiao Bo;Zhang Mengqi
血管生成与脑卒中患者的生存率呈正相关。因此，研究缺血性卒中后启动和促进血管生成的因素对于寻找新的有效治疗靶点以改善卒中预后至关重要。X-box结合蛋白1剪接（X-box binding protein 1 splicing，XBP 1 s）在细胞增殖和血管生成中起着积极的调节作用。然而，XBP 1 s在脑缺血后脑微血管内皮细胞（BMEC）增殖和血管生成中的作用和机制尚不清楚。在目前的研究中，我们研究了XBP 1 s在脑缺血后BMEC增殖和血管生成中的作用。在这项研究中，在氧-葡萄糖剥夺（OGD）处理的BMEC中确定了XBP 1对细胞存活、凋亡、周期迁移和血管生成的作用。在0、2、4和6小时暴露于OGD的BMEC中，XBP 1的表达以时间依赖性方式增加。在OGD处理的BMEC中，XBP 1 s的过表达促进细胞存活、细胞周期、迁移和血管生成，并抑制凋亡。此外，在OGD处理的BMEC中，XBP 1 s的过表达促进了细胞周期蛋白D1、基质金属蛋白酶（MMP-2）和MMP-9的表达，但抑制了切割的Caspase-3和切割的Caspase-9的表达。在OGD处理的BMEC中，XBP 1的过表达还促进了缺氧诱导因子1-α、血管内皮生长因子、磷脂酰肌醇-4，5-二磷酸3-激酶、p-AKT、p-mTOR、p-GSK 3 β和p-细胞外信号调节激酶1/2的表达。XBP 1 s沉默的效果与XBP 1 s过表达的效果相反。总之，使用体外OGD模型，我们证明了XBP 1 s可能是缺血性卒中治疗的一个有希望的靶点，以维持BMEC的存活并诱导血管生成。
Angiogenesis is positively correlated with the survival rate of stroke patients. Therefore, studying factors that initiate and promote angiogenesis after ischemic stroke is crucial for finding novel and effective treatment targets that improve the prognosis of stroke. X‐box binding protein l splicing (XBP1s) plays a positive regulatory role in cell proliferation and angiogenesis. However, the role and mechanism of XBP1s on the proliferation of brain microvascular endothelial cells (BMECs) and angiogenesis after cerebral ischemia remains unclear. In the current study, we investigated the role XBP1s plays in BMEC proliferation and angiogenesis following cerebral ischemia. In this study, the roles of XBP1s on cell survival, apoptosis, cycle migration, and angiogenesis were determined in oxygen‐glucose deprivation (OGD) treated BMECs. The expression of XBP1s in BMECs, which were exposed to OGD at 0, 2, 4, and 6 hr, increased in a time‐dependent manner. The overexpression of XBP1s promoted cell survival, cell cycle, migration, and angiogenesis of BMECs, and inhibited the apoptosis in OGD‐treated BMECs. In addition, the overexpression of XBP1s promoted the expression of cyclin D1, matrix metalloproteinase (MMP‐2), and MMP‐9, but inhibited cleaved Caspase‐3 and cleaved Caspase‐9 expression in OGD‐treated BMECs. The overexpression of XBP1s also promoted the expression of hypoxia‐inducible factor 1‐alpha, vascular endothelial growth factor, phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, p‐AKT, p‐mTOR, p‐GSK3β, and p‐extracellular signal‐regulated kinase1/2 in OGD‐treated BMECs. The effect of XBP1s silencing was opposite to that of XBP1s overexpression. In conclusion, using an in vitro OGD model, we demonstrated that XBP1s may be a promising target for ischemic stroke therapy to maintain BMECs survival and induce angiogenesis.