Milk fat globule-EGF factor VIII attenuates CNS injury by promoting neural stem cell proliferation and migration after cerebral ischemia.
Milk fat globule-EGF factor VIII attenuates CNS injury by promoting neural stem cell proliferation and migration after cerebral ischemia.
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牛奶脂肪球-EGF因子VIII通过促进脑缺血后的神经干细胞增殖和迁移来减轻中枢神经系统损伤。
DOI：
10.1371/journal.pone.0122833
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Cheyuo C;Aziz M;Yang WL;Jacob A;Zhou M;Wang P
在脑卒中后神经发生的再生过程中激活神经干细胞的介质尚未完全确定。乳脂球-EGF因子VIII（MFG-E8）是一种分泌型糖蛋白，通过与其受体αv β3-整联蛋白结合发挥多种细胞功能。然而，其在脑卒中后调节神经干细胞中的作用尚未确定。因此，我们的目的是揭示MFG-E8是否促进中风期间神经干细胞增殖和迁移。通过短暂大脑中动脉闭塞（tMCAO）在野生型（Wt）和MFG-E8缺陷（Mfge 8-/-）小鼠中诱导中风。市售重组小鼠MFG-E8（rmMFG-E8）用于神经干细胞系的机制试验，而内部制备的重组人MFG-E8（rhMFG-E8）用于tMCAO大鼠体内给药。BrdU法检测重组rmMFG-E8对神经干细胞增殖的影响，transwell迁移实验检测重组rmMFG-E8对神经干细胞迁移的影响。通过qPCR分析细胞周期蛋白D2、p53和netrin-1的表达。我们报道了rhMFG-E8治疗显著改善了tMCAO大鼠模型的神经功能缺损评分、体重减轻和神经干细胞增殖。相反，与经历tMCAO的Wt对应物相比，在Mfge 8-/-小鼠中观察到神经干细胞增殖减少。rmMFG-E8通过αv β3-integrin介导的cyclin D2上调和p53下调来促进小鼠胚胎神经干细胞的增殖。rmMFG-E8还通过αv β3-整合素依赖性方式上调netrin-1促进小鼠胚胎神经干细胞迁移。我们的研究结果表明MFG-E8可以促进神经干细胞的增殖和迁移，因此建立了一个有希望的脑缺血治疗策略。
The mediators in activating neural stem cells during the regenerative process of neurogenesis following stroke have not been fully identified. Milk fat globule-EGF Factor VIII (MFG-E8), a secreted glycoprotein serves several cellular functions by binding to its receptor, αv β3-integrin. However, its role in regulating neural stem cells after stroke has not been determined yet. We therefore, aim to reveal whether MFG-E8 promotes neural stem cell proliferation and migration during stroke. Stroke was induced in wild-type (Wt) and MFG-E8-deficinet (Mfge8-/-) mice by transient middle cerebral artery occlusion (tMCAO). Commercially available recombinant mouse MFG-E8 (rmMFG-E8) was used for mechanistic assays in neural stem cell line, while the in house prepared recombinant human MFG-E8 (rhMFG-E8) was used for in vivo administration into rats with tMCAO. The in vitro effects of recombinant rmMFG-E8 for the neural stem cell proliferation and migration were determined by BrdU and transwell migration assay, respectively. The expression of cyclin D2, p53 and netrin-1, was analyzed by qPCR. We report that the treatment of rhMFG-E8 significantly improved the neurological deficit score, body weight lost and neural stem cell proliferation in a rat model of tMCAO. Conversely, decreased neural stem cell proliferation was observed in Mfge8-/- mice in comparison with the Wt counterparts underwent tMCAO. rmMFG-E8 stimulated the proliferation of mouse embryonic neural stem cells via upregulation of cyclin D2 and downregulation of p53, which is mediated by αv β3-integrin. rmMFG-E8 also promoted mouse embryonic neural stem cell migration via αv β3-integrin dependent manner in upregulating netrin-1. Our findings suggest MFG-E8 to promote neural stem cell proliferation and migration, which therefore establishes a promising therapeutic strategy for cerebral ischemia.
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影响因子：
3.7
作者：
Aziz M;Jacob A;Matsuda A;Wu R;Zhou M;Dong W;Yang WL;Wang P
通讯作者：
Wang P
影响因子：
16.6
作者：
Jiang, Peng;Chen, Chen;Wang, Ruimin;Chechneva, Olga V.;Chung, Seung-Hyuk;Rao, Mahendra S.;Pleasure, David E.;Liu, Ying;Zhang, Quanguang;Deng, Wenbin
通讯作者：
Deng, Wenbin
影响因子：
3.7
作者：
Ajakaiye MA;Jacob A;Wu R;Yang WL;Nicastro J;Coppa GF;Wang P
通讯作者：
Wang P
DOI：
10.4049/jimmunol.1200262
发表时间：
2012-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Aziz M;Matsuda A;Yang WL;Jacob A;Wang P
通讯作者：
Wang P
影响因子：
8.3
作者：
BEDERSON, JB;PITTS, LH;BARTKOWSKI, H
通讯作者：
BARTKOWSKI, H