Evidence map›Paper›PMID 41134423›Full record

ArticleNeurochemical research2025

TGM2 Enhances Hypobaric Hypoxia-mediated Brain Injury Via Regulating NLRP3/GSDMD Signaling.

Ying Yao, Yehao Chen, Yan Li, Jing Wang, Meizi You, Meimei Zhu, Liying Yin, Yifei Wang, Jianfei Jin, Chen Wang and 6 more

Abstract read
PubMed Publisher
In one paragraph

Article in Neurochemical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

16 authors.

Ying Yao *Department of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Yehao Chen *Department of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Yan LiDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Jing WangDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Meizi YouDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Meimei ZhuDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Liying YinDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Yifei WangDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Jianfei JinDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Chen WangDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Zhengzhen HuangDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Xinyan ZhouDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Ziyu ZhuDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Yinqiu YangDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China.
Jianping CaoDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China. jianpingcao2020@126.com.
Xiaoyong MiaoDepartment of Anesthesiology, Naval Medical Center, Naval Military Medical University, No. 338, West Huaihai Road, Changning, Shanghai, 200052, China. lizzy_zhouyan@163.com.

Funding

Cultivation of Discipline Characteristics in Navy Characteristic Medical Center 23TSPY06Excellent Talents Project of Navy Characteristic Medical Center 21TPQN4002Innovative Diagnosis and Treatment Technologies of the Navy Characteristic Medical Center 23TSJS02
6 · The paper itself

Abstract

High-altitude hypoxic brain injury (HHBI) is characterized by neuronal damage. Transglutaminase 2 (TGM2) promotes neuroinflammation and the progression of various brain diseases. This study aimed to investigate the role of TGM2. In vivo HHBI models were established using an animal HH chamber. In vitro HHBI models were established using oxygen-glucose deprivation (OGD). Cytokine release was detected using enzyme-linked immunosorbent assay (ELISA). Protein expression was detected using was detected using western blot. NeuN and IBA1 was expression was detected using immunofluorescence. The co-localization of NLR family pyrin domain containing 3 (NLRP3) was analyzed by fluorescent in situ hybridization (FISH) assay. NLRP3 and TGM2 The interaction between TGM2 and NLRP3 inflammasome was verified using Co-immunoprecipitation (Co-IP) assay. Cytotoxicity of neurons was detected using lactate dehydrogenase (LDH) assay. Neuronal viability was detected using cell counting kit-8 (CCK-8) assay. Neuronal death was determined using terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. We found that HH exposure promoted neuronal inflammation and death, contributing to cognitive impairment in vivo. Moreover, HHBI mediated the upregulation of TGM2. However, TGM2 knockdown significantly restored neuronal functions, manifested by suppressing neuronal inflammation and pyroptosis. TGM2 bound to NLRP3 inflammasome, which precipitated endogenous gasdermin D (GSDMD-N) and promoted the expression of N-terminal of GSDMD (GSDMD-N). However, overexpression of NLRP3 abated the effects of TGM2 and promoted neuroinflammation and neuronal pyroptosis. Conclusions: TGM2 promoted neuronal pyroptosis in HHBI via activating NLRP3/GSDMD signaling, contributing to cognitive impairment. Therefore, targeting TGM2/NLRP3 signaling provide a novel strategy for HHBI.

Indexed as

Brain InjuriesGTP-Binding ProteinsHypoxia, BrainNLR Family, Pyrin Domain-Containing 3 ProteinPhosphate-Binding ProteinsTransglutaminasesAnimalsHypoxiaInflammasomesMaleMiceNeuronsProtein Glutamine gamma Glutamyltransferase 2RatsRats, Sprague-DawleySignal TransductionGTP-Binding ProteinsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseNlrp3 protein, ratPhosphate-Binding ProteinsProtein Glutamine gamma Glutamyltransferase 2Tgm2 protein, ratTransglutaminasesHypobaric hypoxiaNerve painPyroptosisTGM2

Identifiers

PMID41134423

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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.