TSG-6 Protects Against Cerebral Ischemia–Reperfusion Injury via Upregulating Hsp70-1B in Astrocytes

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-03-25 DOI:10.1111/cns.70354

Yewei Qu, Lian Yi, Yushi Tang, Fan Yang, Byron Fei Pan, Shanshan Shi, Changda Qu, Fangqin Li, Shirong Wen, Yujun Pan

{"title":"TSG-6 Protects Against Cerebral Ischemia–Reperfusion Injury via Upregulating Hsp70-1B in Astrocytes","authors":"Yewei Qu, Lian Yi, Yushi Tang, Fan Yang, Byron Fei Pan, Shanshan Shi, Changda Qu, Fangqin Li, Shirong Wen, Yujun Pan","doi":"10.1111/cns.70354","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>This study aimed to investigate the relationship between tumor necrosis factor alpha-induced protein (TNFAIP6/TSG-6) and astrocytes in cerebral ischemia/reperfusion (I/R) injury.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Utilizing in vivo and in vitro cerebral I/R models, cerebral infarct volumes, neurobehavioral outcomes, blood–brain barrier (BBB) permeability, as well as indicators of astrocyte apoptosis, reactivity, and A1 phenotype were assessed to evaluate the effects of recombinant rattus TSG-6 (rrTSG-6) on astrocytes in acute cerebral I/R injury. Following mRNA sequencing of all astrocyte groups, astrocyte apoptosis and reactivity were analyzed through a combined intervention of rrTSG-6 and Apoptozole, a heat shock protein 70-1B (Hsp70-1B) inhibitor, in vitro.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The findings demonstrated that rrTSG-6 significantly reduced cerebral infarct volumes by nearly half, improved neurobehavioral outcomes, mitigated BBB damage, and suppressed the expressions of astrocyte apoptosis markers, reactivity indicators, and A1 phenotype markers. mRNA sequencing revealed that the Hsp70-1B protein level increased to approximately 1.6 times that of the rrTSG-6 non-intervention group. Furthermore, Apoptozole impeded the expressions of astrocyte apoptosis markers, reactivity indicators, and A1 phenotype markers.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>TSG-6 inhibited nuclear factor kappa-B (NF-κB) phosphorylation by upregulating Hsp70-1B in oxygen–glucose deprivation/reoxygenation (OGD/R)-induced astrocytes, thereby exerting a protective effect through anti-apoptotic mechanisms and the suppression of astrocyte reactivity and A1 transformation following cerebral I/R injury.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70354","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70354","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Aims

This study aimed to investigate the relationship between tumor necrosis factor alpha-induced protein (TNFAIP6/TSG-6) and astrocytes in cerebral ischemia/reperfusion (I/R) injury.

Methods

Utilizing in vivo and in vitro cerebral I/R models, cerebral infarct volumes, neurobehavioral outcomes, blood–brain barrier (BBB) permeability, as well as indicators of astrocyte apoptosis, reactivity, and A1 phenotype were assessed to evaluate the effects of recombinant rattus TSG-6 (rrTSG-6) on astrocytes in acute cerebral I/R injury. Following mRNA sequencing of all astrocyte groups, astrocyte apoptosis and reactivity were analyzed through a combined intervention of rrTSG-6 and Apoptozole, a heat shock protein 70-1B (Hsp70-1B) inhibitor, in vitro.

Results

The findings demonstrated that rrTSG-6 significantly reduced cerebral infarct volumes by nearly half, improved neurobehavioral outcomes, mitigated BBB damage, and suppressed the expressions of astrocyte apoptosis markers, reactivity indicators, and A1 phenotype markers. mRNA sequencing revealed that the Hsp70-1B protein level increased to approximately 1.6 times that of the rrTSG-6 non-intervention group. Furthermore, Apoptozole impeded the expressions of astrocyte apoptosis markers, reactivity indicators, and A1 phenotype markers.

Conclusion

TSG-6 inhibited nuclear factor kappa-B (NF-κB) phosphorylation by upregulating Hsp70-1B in oxygen–glucose deprivation/reoxygenation (OGD/R)-induced astrocytes, thereby exerting a protective effect through anti-apoptotic mechanisms and the suppression of astrocyte reactivity and A1 transformation following cerebral I/R injury.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.