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PKM2 from hyperactive neuron aggravate lung injury post-stroke by promoting FOXO3A/TXNIP mitochondria translocation in mice 期刊论文

编号：

3533588E0A04D30FB86317C17D54D6B0
作者：

Cheng, Yahong#^[1]Liu, Dexiang^[2];Zhao, Yijing^[1];Li, Tingting^[1];Zhang, Luyao^[1];Sheng, Haoyu^[1];Liu, Sashuang^[2];Chai, Liwei^[1];Xiao, Yilei(肖以磊)^[3]Xing, Xiaohui(邢晓辉)^[3]Chen, Wenqiang^[4];Wang, Zhen*^[1,5]
语种：

英文
期刊：

REDOX BIOLOGY ISSN：2213-2317 2026 年 91 卷 ; APR
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关键词：

Ischemic stroke Neuronal activity Mitochondria PKM2 Extracellular vesicles Lung injury
摘要：

Ischemic stroke patients frequently develop acute lung injury (ALI), but the pathogenesis of stroke-induced ALI remains elusive. While reperfusion therapy improves stroke survival, it fails to mitigate systemic complications. Therefore, clarifying mechanisms, identifying predictors, and developing distal-targeted therapies for strokeassociated lung injury are unmet medical need. Here, we identified the serum pyruvate kinase M2 (PKM2), a modulator of systemic inflammation, exhibit predictive value for assessing severity and outcomes of stroke patients. Using a mouse model of ischemic stroke, circulating PKM2 derived from neural hyperactivity in the ipsilesional primary motor cortex (M1) was found to be related to stroke-induced ALI. Mechanistically, PKM2 loaded in extracellular vesicles (EVs) from activated neurons target alveolar epithelial cells (AEC) via blood circulating and bind to Forkhead Box O3 (FOXO3A), induce its S252 phosphorylation, and promote PKM2/ FOXO3A/thioredoxin-interacting protein (TXNIP) mitochondria translocation and reactive oxygen species production in mouse AEC. Finally, a pulmonary surfactant liposome loaded with interfering peptide are designed to target and disrupt PKM2-FOXO3A interaction exerting lung protective effects in a mouse model of ischemic stroke. Summarily, PKM2 from activated neurons mediates intercellular crosstalk between brain-lung via host target proteins FOXO3A/TXNIP, contributing to AEC mitochondrial dysfunction and stroke-induced ALI.
推荐引用方式
GB/T 7714：

Cheng Yahong,Liu Dexiang,Zhao Yijing, et al. PKM2 from hyperactive neuron aggravate lung injury post-stroke by promoting FOXO3A/TXNIP mitochondria translocation in mice [J].REDOX BIOLOGY,2026,91.
APA：

Cheng Yahong,Liu Dexiang,Zhao Yijing,Li Tingting,&Wang Zhen.(2026).PKM2 from hyperactive neuron aggravate lung injury post-stroke by promoting FOXO3A/TXNIP mitochondria translocation in mice .REDOX BIOLOGY,91.
MLA：

Cheng Yahong, et al. "PKM2 from hyperactive neuron aggravate lung injury post-stroke by promoting FOXO3A/TXNIP mitochondria translocation in mice" .REDOX BIOLOGY 91(2026).
入库时间：

3/18/2026 9:21:06 PM
更新时间：

3/18/2026 9:21:06 PM

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