Prdx1 Reduces Intracerebral Hemorrhage-Induced Brain Injury via Targeting Inflammation- and Apoptosis-Related mRNA Stability
Guoqiang Yang, Jiacheng Huang, Junjie Yuan, Qin Zhang, Chang‐Xiong Gong, Qiong Chen, Qi Xie, Lexing Xie, Ru Chen, Zhongming Qiu, Kai Zhou, Rui‐Hua Xu, Guohui Jiang, Xiao‐Yi Xiong, Qingwu Yang
Abstract
RNA-binding proteins (RBPs) have been shown to be involved in posttranscriptional regulation, which plays an important role in the pathophysiology of intracerebral hemorrhage (ICH). Peroxiredoxin 1 (Prdx1), an RBP, plays an important role in regulating inflammation and apoptosis. Given that inflammation and apoptosis could contribute to ICH-induced brain injury. Therefore, in this study, using ICH models coupled with in vitro experiments, we investigated the role and mechanisms of Prdx1 in regulating inflammation and apoptosis by acting as an RBP after ICH. We first found that Prdx1 was significantly up-regulated in response to ICH-induced brain injury and was mainly expressed in astrocytes and microglia in ICH rat brains. After overexpressing Prdx1 by injecting adeno-associated virus (AAV) into the striatum of rats at 3 weeks, we constructed ICH models and found that Prdx1 overexpression markedly reduced inflammation and apoptosis after ICH. Furthermore, RNA immunoprecipitation combined with high-throughput sequencing (RIP-seq) in vitro revealed that Prdx1 affects the stability of inflammation- and apoptosis-related mRNA, resulting in inhibition of inflammation and apoptosis. Finally, overexpression of Prdx1 significantly alleviated the symptoms and mortality of rats subjected to ICH. Our results show that Prdx1 reduces ICH-induced brain injury by targeting inflammation- and apoptosis-related mRNA stability. Prdx1 may be an improved therapeutic target for alleviating the brain injury caused by ICH.