Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury

Lou,Zheng; Wang,Ai‑Ping; Duan,Xiao‑Ming; Hu,Guo‑Huang; Zuo,Mei‑Ling; Yang,Zhong‑Bao

doi:10.3892/etm.2018.6377

Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury

Authors:
- Zheng Lou
- Ai‑Ping Wang
- Xiao‑Ming Duan
- Guo‑Huang Hu
- Mei‑Ling Zuo
- Zhong‑Bao Yang
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Affiliations: Key Laboratory Breeding Base of Hunan Oriented Fundamental and Applied Research of Innovative Pharmaceutics, Changsha Medical University, Changsha, Hunan 410219, P.R. China, Department of Anatomy, School of Medicine, University of South China, Hengyang, Hunan 421001, P.R. China, Department of Pharmacy, The Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan 410006, P.R. China
Published online on: June 29, 2018 https://doi.org/10.3892/etm.2018.6377
Pages: 1671-1678
Copyright: © Lou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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