Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury.
Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury.
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ALK5/SMAD2/3信号在脑缺血/再灌注损伤中NOX表达调控中的作用
DOI：
10.3892/etm.2018.6377
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发表时间：
2018-09
影响因子：
2.7
通讯作者：
Yang ZB
中科院分区：
文献类型：
--
作者：
Lou Z;Wang AP;Duan XM;Hu GH;Zuo ML;Yang ZB
烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX）源性活性氧（ROS）在脑缺血/再灌注（I/R）损伤中起重要作用。然而，ROS产生的调节机制尚未完全阐明。本研究旨在探讨转化生长因子-β信号通路在ROS产生中的作用。Sprague道利大鼠I/R损伤后，PC-12细胞转染小分子干扰RNA（siRNA），以抑制活化素受体样激酶（ALK）5或缺氧/复氧（H/R）。结果表明，缺血/再灌注或缺氧/再灌注可显著增加ALK 5的表达、SMAD 2/3的磷酸化和NOX 2/4的表达及活性，并伴随着ROS的产生和细胞凋亡。此外，ALK 5敲低显著逆转了PC-12细胞中H/R处理诱导的变化。这些结果表明ALK 5/SMAD 2/3信号传导在氧化应激中发挥关键作用。据我们所知，这是第一项证明ALK 5/SMAD 2/3激活与NOX 2/4表达调节相关并加剧I/R损伤的研究。
Nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) serve an important role in cerebral ischemia/reperfusion (I/R) injury. However, the mechanism by which ROS generation is regulated has not yet been fully elucidated. The present study aimed to explore the role of transforming growth factor-β signaling in ROS generation. Sprague Dawley rats were subjected to I/R injury and PC-12 cells were transfected with small interfering RNA against activin receptor-like kinase (ALK)5 or hypoxia/reoxygenation (H/R). The results indicated that I/R or H/R significantly increased ALK5 expression, SMAD2/3 phosphorylation and NOX2/4 expression and activity, concomitant with ROS generation and apoptosis. In addition, ALK5 knockdown significantly reversed changes induced by H/R treatment in PC-12 cells. These results suggest that ALK5/SMAD2/3 signaling serves a key role in oxidative stress. To the best of our knowledge, this is the first study to demonstrate that ALK5/SMAD2/3 activation is associated with the regulation of NOX2/4 expression and exacerbates I/R injury.
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