miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury

Author:

He Liufang1ORCID,Wei Tingyan1,Huang Yong1,Zhang Xueli1,Zhu Dongbo1,Liu Huazhen2ORCID,Wang Zhangxing1ORCID

Affiliation:

1. Department of Neonatology, Affiliated Longhua People’s Hospital, Southern Medical University (Longhua People’s Hospital), Shenzhen, Guangdong 518190, China

2. Section of Immunology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China

Abstract

White matter injury (WMI) is the most frequent impairment of neurodevelopment in preterm infants. Here, we report that the caspase-1 inflammasome is abundantly activated in the microglia of WMI mice and results in increased pyroptosis of microglia. Pharmacology inhibition of caspase-1 cleavage alleviated the pathogenesis of WMI mice. The expression of microRNA miR-214-3p was largely reduced in the microglia of WMI mice compared to controls. Compromised expression of miR-214-3p on microglia gives rise to the inflammasome activation and microglial pyroptosis. Treatment with miR-214-3p agomir is sufficient to relieve the white matter lesion and demyelination in WMI mice. miR-214-3p is able to bind to the 3 region of the NLRP-3 inflammasome compartment NEK7, preventing the transcription of NEK7 mRNA. As a result, in WMI mice, the lack of miR-214-3p leads to the accumulation of NEK7 which supports NLRP 3 inflammasome activation, microglial pyroptosis, and white matter pathogenesis.

Funder

Shenzhen Science and Technology Innovation Commission

Publisher

Hindawi Limited

Subject

Immunology,General Medicine,Immunology and Allergy

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