Neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-κB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice.
Neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-κB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice.
复制标题
神经元源性 FGF10 通过抑制 NF-κ B 依赖性神经炎症和激活 PI3K/Akt 存活信号通路改善小鼠脑缺血损伤
DOI：
10.1038/srep19869
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发表时间：
2016-01-27
影响因子：
4.6
通讯作者：
Yuan HB
中科院分区：
文献类型：
--
作者：
Li YH;Fu HL;Tian ML;Wang YQ;Chen W;Cai LL;Zhou XH;Yuan HB
FGF10 是成纤维细胞生长因子 (FGF) 的成员。我们之前在体外证明 FGF10 可以保护神经元免受氧糖剥夺损伤；然而，FGF10 在体内缺血性中风中的作用尚不清楚。在本研究中，我们发现FGF10主要在神经元而非星形胶质细胞中表达，并在小鼠脑脊液中检测到FGF10。神经元培养基和细胞裂解物中的FGF10水平远高于星形胶质细胞中的水平。在小鼠大脑中动脉闭塞（MCAO）模型中，脑组织中的 FGF10 表达和脑脊液中的 FGF10 水平增加。将FGF10注入侧脑室不仅可以减少MCAO诱导的脑梗塞体积和神经功能缺损，而且还可以减少TUNEL阳性细胞的数量和Caspase的活性。此外，FGF10治疗抑制了触发的炎症因子（TNF-α和IL-6）和NF-κB信号通路，并增加了PI3K/Akt信号通路的磷酸化。渥曼青霉素和 Akt1/2 激酶抑制剂阻断 PI3K/Akt 信号通路，部分损害了 FGF10 的神经保护作用。然而，阻断 PI3K/Akt 信号通路并不会损害 FGF10 的抗炎作用。总的来说，我们的结果表明，神经元源性 FGF10 通过抑制 NF-κB 依赖性神经炎症和激活 PI3K/Akt 存活信号通路来改善小鼠脑缺血损伤。
FGF10 is a member of fibroblast growth factors (FGFs). We previously showed that FGF10 protects neuron against oxygen-glucose deprivation injury in vitro; however, the effect of FGF10 in ischemic stroke in vivo is unknown. In the present study, we showed that FGF10 was mainly expressed in neurons but not astrocytes, and detected FGF10 in mouse cerebrospinal fluid. The FGF10 levels in neurons culture medium and cell lysate were much higher than those in astrocytes. FGF10 expression in brain tissue and FGF10 level in CSF were increased in mouse middle cerebral artery occlusion (MCAO) model. Administration of FGF10 into lateral cerebroventricle not only decreased MCAO-induced brain infarct volume and neurological deficit, but also reduced the number of TUNEL-positive cells and activities of Caspases. Moreover, FGF10 treatment depressed the triggered inflammatory factors (TNF-α and IL-6) and NF-κB signaling pathway, and increased phosphorylation of PI3K/Akt signaling pathway. Blockade of PI3K/Akt signaling pathway by wortmannin and Akt1/2-kinase inhibitor, partly compromised the neuroprotection of FGF10. However, blockade of PI3K/Akt signaling pathway did not impair the anti-inflammation action of FGF10. Collectively, our results demonstrate that neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-κB-dependent neuroinflammation and activating PI3K/Akt survival signaling pathway in mice.