microRNA-137 promotes endothelial progenitor cell proliferation and angiogenesis in cerebral ischemic stroke mice by targeting NR4A2 through the Notch pathway (Retracted Article)
microRNA-137 promotes endothelial progenitor cell proliferation and angiogenesis in cerebral ischemic stroke mice by targeting NR4A2 through the Notch pathway (Retracted Article)
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DOI：
10.1002/jcp.26312
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发表时间：
2018-07-01
影响因子：
5.6
通讯作者：
Lyu, Liang
中科院分区：
文献类型：
--
作者：
Liu, Xing-Li;Wang, Gang;Lyu, Liang
缺血性脑卒中（CIS）是世界范围内导致死亡和残疾的常见原因之一。本研究旨在通过Notch通路靶向NR4A2，探讨miR-137对CIS内皮祖细胞和血管生成的影响。取CIS小鼠和正常小鼠的脑组织。免疫组化法检测NR4A2表达阳性率。ELISA法检测血清VEGF、Ang、HGF、IB水平。RT-qPCR和Western blotting检测相关因子的表达。将CIS小鼠内皮祖细胞处理后分为空白组、NC组、miR-137模拟物组、miR-137抑制剂组、siRNA-NR4A2组和miR-137抑制剂+siRNA-NR4A2组，正常小鼠细胞分为正常组。MTT和流式细胞术分别检测细胞增殖和细胞凋亡。NR4A2蛋白在CIS小鼠中呈强阳性表达，血清VEGF、Ang、HGF水平高于正常小鼠，IB水平低于正常小鼠。与正常组相比，其余各组（CIS小鼠内皮祖细胞）miR-137、Hes1、Hes5和IB的表达降低，而NR4A2、Notch、Jagged1、Hey-2、VEGF、Ang和HGF的表达升高，增殖受到抑制，细胞凋亡增强。与空白组和NC组相比，miR-137 mimic组和siRNA-NR4A2组miR-137、Hes1、Hes5和IB的表达增加，而NR4A2、Notch、Jagged1和Hey-2的表达减少，增殖增强，凋亡减弱。miR-137抑制剂组逆转了这些情况。miR-137通过Notch信号通路靶向NR4A2，促进CIS小鼠内皮祖细胞增殖和血管生成。
Cerebral ischemic stroke (CIS) is one of the common causes of death and disability worldwide. This study aims to investigate effect of miR-137 on endothelial progenitor cells and angiogenesis in CIS by targeting NR4A2 via the Notch pathway. Brain tissues were extracted from CIS and normal mice. Immunohistochemistry was used to determine positive rate of NR4A2 expression. Serum VEGF, Ang, HGF, and IB levels were determined by ELISA. RT-qPCR and Western blotting were used to determine expression of related factors. Endothelial progenitor cells in CIS mice were treated and grouped into blank, NC, miR-137 mimic, miR-137 inhibitor, siRNA-NR4A2, and miR-137 inhibitor+siRNA-NR4A2 groups, and cells in normal mice into normal group. Proliferation and apoptosis were determined by MTT and flow cytometry, respectively. NR4A2 protein expression was strongly positive in CIS mice, which showed higher serum levels of VEGF, Ang, and HGF but lower IB than normal mice. Compared with normal group, the rest groups (endothelial progenitor cells from CIS mice) showed decreased expressions of miR-137, Hes1, Hes5, and IB but elevated NR4A2, Notch, Jagged1, Hey-2, VEGF, Ang, and HGF, inhibited proliferation and enhanced apoptosis. Compared with blank and NC groups, the miR-137 mimic and siRNA-NR4A2 groups exhibited increased expression of miR-137, Hes1, Hes5, and IB, but decreased NR4A2, Notch, Jagged1, and Hey-2, with enhanced proliferation and attenuated apoptosis. The miR-137 inhibitor group reversed the conditions. miR-137 enhances the endothelial progenitor cell proliferation and angiogenesis in CIS mice by targeting NR4A2 through the Notch signaling pathway.