Evidence map›Paper›PMID 41707616›Full record

ArticleRedox biology2026

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

Yahong Cheng, Dexiang Liu, Yijing Zhao, Tingting Li, Luyao Zhang, Haoyu Sheng, Sashuang Liu, Liwei Chai, Yilei Xiao, Xiaohui Xing and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Yahong ChengDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Dexiang LiuDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Yijing ZhaoDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Tingting LiDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Luyao ZhangDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Haoyu ShengDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Sashuang LiuDepartment of Medical Psychology and Ethics, School of Basic Medicine Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Liwei ChaiDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China.
Yilei XiaoDepartment of Neurosurgery, Liaocheng Neuroscience Laboratory, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, PR China.
Xiaohui XingDepartment of Neurosurgery, Liaocheng Neuroscience Laboratory, Liaocheng People's Hospital, Liaocheng, Shandong, 252000, PR China.
Wenqiang ChenQilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, PR China.
Zhen WangDepartment of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, PR China. Electronic address: wangzhen@sdu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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 stroke-associated 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.

Indexed as

Acute Lung InjuryCarrier ProteinsForkhead Box Protein O3MitochondriaNeuronsPyruvate KinaseStrokeAnimalsDisease Models, AnimalExtracellular VesiclesHumansMaleMiceCarrier ProteinsForkhead Box Protein O3FoxO3 protein, mousePkm protein, mousePyruvate KinaseExtracellular vesiclesIschemic strokeLung injuryMitochondriaNeuronal activityPKM2

Identifiers

PMID41707616
PMCPMC12927099

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.