Follistatin-like 1 attenuates apoptosis via disco-interacting protein 2 homolog A/Akt pathway after middle cerebral artery occlusion in rats.
Follistatin-like 1 attenuates apoptosis via disco-interacting protein 2 homolog A/Akt pathway after middle cerebral artery occlusion in rats.
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DOI：
10.1161/strokeaha.114.006092
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发表时间：
2014-10
期刊：
影响因子：
8.3
通讯作者：
Zhang JH
中科院分区：
文献类型：
--
作者：
Liang X;Hu Q;Li B;McBride D;Bian H;Spagnoli P;Chen D;Tang J;Zhang JH
据报道，卵泡抑素样 1 (FSTL1) 是一种细胞外糖蛋白，可减少缺血性心脏病中的细胞凋亡，但其在缺血性中风中的作用尚未得到检验。我们假设重组 FSTL1 通过其受体 DIP2A 和 Akt 通路减轻大鼠大脑中动脉闭塞 (MCAO) 后的神经元凋亡。对 140 只雄性 Sprague-Dawley 大鼠进行 2 小时的 MCAO，然后进行再灌注。在一部分动物中，通过蛋白质印迹和免疫荧光双染色检测 FSTL1 和 DIP2A 的时间过程和位置。另一组动物在再灌注后1小时脑室内给予重组FSTL1或在再灌注前48小时脑室内给予FSTL1-siRNA。此外，DIP2A 在一些动物中被 siRNA 敲低。测量梗塞体积和神经功能缺损，并使用蛋白质印迹定量 FSTL1、DIP2A、磷酸化 Akt、cleaved caspase-3 和 TUNEL 的表达。神经元中 FSTL1 和 DIP2A 的表达增加，并在 MCAO 后 24 小时达到峰值。重组 FSTL1 通过激活其受体 DIP2A 和下游 Akt 磷酸化，减少了脑梗塞并改善了 MCAO 后 24 小时和 72 小时的神经功能缺损。 DIP2A-siRNA 和 FSTL1-siRNA 逆转了这些效应。在大鼠 MCAO 后，重组 FSTL1 通过激活其受体 DIP2A 来磷酸化 Akt，从而减少神经元凋亡并改善神经功能缺损。因此，FSTL1可能具有治疗缺血性中风患者的潜力。
Follistatin-like 1 (FSTL1), an extracellular glycoprotein, has been reported to decrease apoptosis in ischemic cardiac diseases but its effect in ischemic stroke has not been examined. We hypothesized that recombinant FSTL1 attenuates neuronal apoptosis through its receptor DIP2A and the Akt pathway after middle cerebral artery occlusion (MCAO) in rats. One hundred and forty male Sprague-Dawley rats were subjected to 2 hours of MCAO followed by reperfusion. In a subset of animals, the time course and location of FSTL1 and DIP2A were detected by western blot and immunofluorescence double staining. Another set of animals were intracerebroventricularly given either recombinant FSTL1 1 hour after reperfusion or FSTL1-siRNA 48 hours before reperfusion. Additionally, DIP2A was knockdown by siRNA in some animals. Infarction volume and neurological deficits were measured, and the expression of FSTL1, DIP2A, phosphorylated Akt, cleaved caspase-3 and TUNEL were quantified using Western blot. The expression of FSTL1 and DIP2A were increased in neurons and peaked 24 hours after MCAO. Recombinant FSTL1 reduced brain infarction and improved neurologic deficits 24 and 72 hours after MCAO via activation of its receptor DIP2A and downstream phosphorylation of Akt. These effects were reversed by DIP2A-siRNA and FSTL1-siRNA. Recombinant FSTL1 decreases neuronal apoptosis and improves neurological deficits through phosphorylation of Akt by activation of its receptor DIP2A after MCAO in rats. Thus, FSTL1 may have potentials as a treatment for ischemic stroke patients.