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CHRFAM7A Overexpression Attenuates Cerebral Ischemia-Reperfusion Injury via Inhibiting Microglia Pyroptosis Mediated by the NLRP3/Caspase-1 pathway

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Abstract

Cerebral ischemia-reperfusion (I/R) injury is an inflammation-related disease. CHRFAM7A can regulate inflammatory responses. Therefore, the present study investigated the mechanism of CHRFAM7A in cerebral I/R injury. CHRFAM7A expression and inflammatory cytokine levels in patients with cerebral I/R injury and oxygen-glucose deprivation/reperfusion (OGD/R)-treated microglia were detected. The proliferation, inflammatory cytokine expressions, nod-like receptor protein 3 (NLRP3) level, cell pyroptosis, and viability and lactate dehydrogenase (LDH) activity in OGD/R-treated microglia were detected after CHRFAM7A overexpression. The NLRP3/Caspase-1 pathway was activated to assess the effect of CHRFAM7A on microglia. Expressions of microglial M1 phenotype marker iNOS and M2 marker Arg1 were detected. Downregulated CHRFAM7A and elevated inflammatory cytokine levels were observed in patients with cerebral I/R injury and OGD/R-treated microglia. In OGD/R-treated microglia, CHRFAM7A overexpression promoted cell proliferation and viability, reduced inflammation and LDH activity, and inhibited NLRP3 inflammasome activation and cell pyroptosis. Mechanically, CHRFAM7A inhibited microglia pyroptosis via inhibiting the NLRP3/Caspase-1 pathway and reduced cell inflammatory injury via promoting microglia polarization from M1 to M2. Overall, CHRFAM7A overexpression attenuated cerebral I/R injury by inhibiting microglia pyroptosis in a NLRP3/Caspase-1 pathway-dependent manner and promoting microglia polarization to M2 phenotype.

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Author notes

  1. Xiangyuan Cao and Yida Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Shanghai Tenth People’s Hospital, Clinical Medical College of Nanjing Medical University, No. 301 Yanchangzhong Road, Shanghai, 200072, China

    Xiangyuan Cao & Liang Gao

  2. Department of Neurosurgery, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

    Yida Wang

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  1. Xiangyuan Cao
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  2. Yida Wang
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Contributions

Conceptualization: XC. Validation, research, resources, data reviewing, and writing: XC and YW. Review and editing: LG. All authors read and approved the final manuscript.

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Correspondence to Liang Gao.

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This study was performed with the approval of the Clinical Ethical Committee of Shanghai Tenth People’s Hospital. All study subjects signed written informed consents. All procedures were strictly conducted in accordance with the code of ethics.

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Cao, X., Wang, Y. & Gao, L. CHRFAM7A Overexpression Attenuates Cerebral Ischemia-Reperfusion Injury via Inhibiting Microglia Pyroptosis Mediated by the NLRP3/Caspase-1 pathway. Inflammation 44, 1023–1034 (2021). https://doi.org/10.1007/s10753-020-01398-4

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