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

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机构: [1]Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China [2]Stomatology Hospital, School of Stomatology, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Zhejiang University School of Medicine, Hangzhou 310006, China [3]Department of Prosthodontics, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing 100081, China [4]Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812‑8582, Japan [5]Department of Neurology, West China Hospital, Sichuan University, Chengdu 610041, China [6]Department of Physiology, Nihon University School of Dentistry, Tokyo 101‑8310, Japan [7]Department of Pharmacology, Faculty of Pharmacy, Yasuda Women’s University, Hiroshima 731‑0153, Japan
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关键词: Protease-activated receptor 2 Microglia Neuron Hypoxic-ischemic injury

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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.© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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出版当年[2021]版:
大类 | 2 区 医学
小类 | 2 区 神经科学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 神经科学
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第一作者机构: [1]Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China [2]Stomatology Hospital, School of Stomatology, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Zhejiang University School of Medicine, Hangzhou 310006, China
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