bFGF Protects Against Blood-Brain Barrier Damage Through Junction Protein Regulation via PI3K-Akt-Rac1 Pathway Following Traumatic Brain Injury.
bFGF Protects Against Blood-Brain Barrier Damage Through Junction Protein Regulation via PI3K-Akt-Rac1 Pathway Following Traumatic Brain Injury.
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BFGF在创伤性脑损伤后通过PI3K-AKT-RAC1途径来防止通过连接蛋白调节血脑屏障损伤。
DOI：
10.1007/s12035-015-9583-6
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发表时间：
2016-12
影响因子：
5.1
通讯作者：
Xiao J
中科院分区：
文献类型：
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作者：
Wang ZG;Cheng Y;Yu XC;Ye LB;Xia QH;Johnson NR;Wei X;Chen DQ;Cao G;Fu XB;Li XK;Zhang HY;Xiao J
由于缺乏明确的治疗方法来减少颅脑损伤引起的血脑屏障(BBB)的破坏，许多创伤性脑损伤(TBI)幸存者患有神经残疾和认知障碍。外源性碱性成纤维细胞生长因子在脑损伤中具有神经保护作用。因此，本研究旨在探讨碱性成纤维细胞生长因子对颅脑损伤后血脑屏障的保护作用及其机制。在这项研究中，我们证明了碱性成纤维细胞生长因子减少了脑外伤小鼠的神经功能缺陷，并保持了血脑屏障的完整性。碱性成纤维细胞生长因子抑制RhoA并上调紧密连接蛋白，从而减轻血脑屏障的破坏。在体外，碱性成纤维细胞生长因子通过上调缺氧缺糖/复氧状态下人脑微血管内皮细胞紧密连接蛋白claudin-5、occludin、zonula occludens-1、p120-catenin和β-catenin对血脑屏障起到保护作用。体内和体外的作用都与下游信号通路PI3K/Akt/Rac-1的激活有关。分别用特异性抑制剂LY294002或si-RAC-1抑制PI3K/Akt或RAC-1，可部分减弱bFGF对BBB完整性的保护作用。综上所述，我们的研究结果表明，碱性成纤维细胞生长因子对血脑屏障的保护作用涉及对脑创伤模型中紧密连接蛋白和RhoA的调节以及OGD诱导的HBMECs损伤，而PI3K/Akt/Rac-1信号通路的激活是这些作用的基础。
Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced blood-brain barrier (BBB) breakdown. Exogenous basic fibroblast growth factor (bFGF) has been shown to have neuroprotective function in brain injury. The present study therefore investigates the beneficial effects of bFGF on the BBB after TBI and the underlying mechanisms. In this study, we demonstrate that bFGF reduces neurofunctional deficits and preserves BBB integrity in a mouse model of TBI. bFGF suppresses RhoA and upregulates tight junction proteins, thereby mitigating BBB breakdown. In vitro, bFGF exerts a protective effect on BBB by upregulating tight junction proteins claudin-5, occludin, zonula occludens-1, p120-catenin, and β-catenin under oxygen glucose deprivation/reoxygenation (OGD) in human brain microvascular endothelial cells (HBMECs). Both the in vivo and in vitro effects are related to the activation of the downstream signaling pathway, PI3K/Akt/Rac-1. Inhibition of the PI3K/Akt or Rac-1 by specific inhibitors LY294002 or si-Rac-1, respectively, partially reduces the protective effect of bFGF on BBB integrity. Overall, our results indicate that the protective role of bFGF on BBB involves the regulation of tight junction proteins and RhoA in the TBI model and OGD-induced HBMECs injury, and that activation of the PI3K/Akt/Rac-1 signaling pathway underlies these effects.
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影响因子：
8.3
作者：
GARCIA, JH;WAGNER, S;HU, XJ
通讯作者：
HU, XJ
影响因子：
3.7
作者：
Hossain MS;Ifuku M;Take S;Kawamura J;Miake K;Katafuchi T
通讯作者：
Katafuchi T
影响因子：
4.2
作者：
Luo, Cheng-Liang;Chen, Xi-Ping;Tao, Lu-Yang
通讯作者：
Tao, Lu-Yang
影响因子：
15.9
作者：
Murakami, Masahiro;Nguyen, Loc T.;Simons, Michael
通讯作者：
Simons, Michael
影响因子：
8.8
作者：
通讯作者：
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