Differential Expression and Distinct Roles of Proteinase-Activated Receptor 2 in Microglia and Neurons in Neonatal Mouse Brain After Hypoxia-Ischemic Injury

Yicong Liu, Hui Li, Jiangqi Hu, Zhou Wu, Jie Meng, Yoshinori Hayashi, Hiroshi Nakanishi, Hong Qing, Junjun Ni

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Regulation of microglial activation and neuroinflammation are critical factors in the pathogenesis of ischemic brain injury. Interest in protease-activated receptor 2 (PAR2) as a pharmaceutical target for various diseases is creasing. However, it is unclear the expression and functions of PAR2 in hypoxia-ischemic (HI) brain injury. Mice with HI and cells with oxygen–glucose deprivation and reoxygenation (OGD/R) were studied. Immunoblot and qRT-PCR were used to study the differential gene expression in cultured microglia and neurons. Immunofluorescent staining was used to study the expression pattern of PAR2 in the HI brain and phagocytotic activity of microglia after OGD/R. In neonatal mice brain after HI, we found PAR2 expression was abundant in neurons, but barely in microglia from the contralateral side of cortex and hippocampus. Conversely, PAR2 expression was barely in neurons while significantly increased in activated microglia from the ipsilateral side of cortex and hippocampus. The activations of PAR2 were increased in both microglia and neuron in a cell model of OGD/R. PAR2 activation mediated the cross-talk between microglia and neurons including the following: microglial PAR2 mediated inflammatory responses that induced neuronal damage; neuronal PAR2 regulated chemokines that recruited activated microglia to damage area; microglia PAR2 controlled the phagocytosis of degenerating neurons. These data suggested differential expression and distinct roles of PAR2 in microglia and neurons after HI injury; thereby, interventions targeting PAR2 may provide insights into the inflammatory-related diseases.

本文言語英語
ページ(範囲)717-730
ページ数14
ジャーナルMolecular Neurobiology
59
1
DOI
出版ステータス出版済み - 1月 2022

!!!All Science Journal Classification (ASJC) codes

  • 神経学
  • 細胞および分子神経科学

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