He Liufang, Wei Tingyan, Huang Yong, Zhang Xueli, Zhu Dongbo, Liu Huazhen, Wang Zhangxing
Department of Neonatology, Affiliated Longhua People's Hospital, Southern Medical University (Longhua People's Hospital), Shenzhen, Guangdong 518190, China.
Section of Immunology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China.
J Immunol Res. 2022 Aug 22;2022:1642896. doi: 10.1155/2022/1642896. eCollection 2022.
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.
白质损伤（WMI）是早产儿神经发育中最常见的损伤。在此，我们报告胱天蛋白酶-1炎性小体在WMI小鼠的小胶质细胞中大量激活，并导致小胶质细胞焦亡增加。胱天蛋白酶-1切割的药理学抑制减轻了WMI小鼠的发病机制。与对照组相比，WMI小鼠小胶质细胞中微小RNA miR-214-3p的表达大幅降低。小胶质细胞中miR-214-3p表达受损导致炎性小体激活和小胶质细胞焦亡。用miR-214-3p激动剂治疗足以缓解WMI小鼠的白质损伤和脱髓鞘。miR-214-3p能够与NLRP-3炎性小体隔室NEK7的3'区域结合，阻止NEK7 mRNA的转录。因此，在WMI小鼠中，miR-214-3p的缺乏导致NEK7的积累，这支持NLRP 3炎性小体激活、小胶质细胞焦亡和白质发病机制。
