Vinexin- deficiency protects against cerebral ischaemia/reperfusion injury by inhibiting neuronal apoptosis
Vinexin- deficiency protects against cerebral ischaemia/reperfusion injury by inhibiting neuronal apoptosis
复制标题
Vinexin- 缺乏通过抑制神经元凋亡来预防脑缺血/再灌注损伤
DOI：
10.1111/jnc.13110
复制
发表时间：
2015
影响因子：
4.7
通讯作者：
Li Hongliang
中科院分区：
文献类型：
--
作者：
Li Mingchang;Guo Sen;Zhang Peng;Gong Jun;Zheng Ankang;Zhang Yan;Li Hongliang
Vinexin-β是一种调节细胞粘附、细胞骨架组织和信号转导的衔接蛋白。我们以前的工作表明，Vinexin‐β可以防止心脏肥大。然而，其在中风中的功能在很大程度上是未知的。在本研究中，我们观察到Vinexin-β在人脑出血和小鼠脑缺血/再灌注（I/R）损伤模型中的表达显著增加，表明Vinexin-β参与了卒中。接下来，使用Vinexin-β敲除小鼠，我们进一步证明Vinexin-β缺乏显著保护脑I/R损伤，如梗死体积急剧减少和神经功能改善所示。此外，免疫荧光和蛋白质印迹显示，Vinexin-β的缺失减弱了神经元凋亡。从机制上讲，我们发现缺血性损伤后，与WT对照小鼠相比，Vinexin-β敲除小鼠脑中Akt信号传导上调。综上所述，我们的结果表明，Vinexin-β的缺失通过抑制神经元凋亡有效地保护缺血性损伤，并且这种作用可能通过Akt信号转导的上调而发生。我们的研究结果表明，Vinexin-β作为缺血性损伤的一种新的调节剂，这表明Vinexin-β可能是预防中风的一个有吸引力的治疗靶点。 Vinexin-β是一种调节细胞粘附和细胞骨架组织的衔接蛋白。我们发现，Vinexin-β-缺陷小鼠对缺血/再灌注（I/R）损伤具有有效的保护作用。保护作用是通过抑制神经元凋亡介导的，这可能通过Akt信号转导的上调发生。这些发现表明Vinexin-β是I/R损伤的新型调节剂，也是预防卒中的有吸引力的治疗靶点。
Vinexin‐β is an adaptor protein that regulates cell adhesion, cytoskeletal organization and signal transduction. Our previous work showed that Vinexin‐β protects against cardiac hypertrophy. However, its function in stroke is largely unknown. In the present study, we observed a significant increase in Vinexin‐β expression in both human intracerebral haemorrhage and mouse cerebral ischaemia/reperfusion (I/R) injury model, indicating that Vinexin‐β is involved in stroke. Next, using Vinexin‐β knockout mice, we further demonstrated that Vinexin‐β deficiency significantly protected against cerebral I/R injury, as demonstrated by a dramatic decrease in the infarct volume and an improvement in neurological function. Additionally, immunofluorescence and western blotting showed that the deletion of Vinexin‐β attenuated neuronal apoptosis. Mechanically, we found that Akt signalling was up‐regulated in the brains of the Vinexin‐β knockout mice compared with those of the WT control mice after ischaemic injury. Taken together, our results demonstrate that the deletion of Vinexin‐β potently protects against ischaemic injury by inhibiting neuronal apoptosis, and this effect may occur via the up‐regulation of Akt signalling. Our findings revealed that Vinexin‐β acts as a novel modulator of ischaemic injury, suggesting that Vinexin‐β may represent an attractive therapeutic target for the prevention of stroke. Vinexin‐β is an adaptor protein that regulates cell adhesion and cytoskeletal organization. We revealed that Vinexin‐β‐deficient mice are potently protected against ischaemia/reperfusion (I/R) injury. The protective effect is mediated through inhibiting neuronal apoptosis, which may occur via the up‐regulation of Akt signalling. These findings suggest Vinexin‐β as a novel regulator of I/R injury and attractive therapeutic target for the prevention of stroke.