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Inhibition of microRNA‐199a‐5p ameliorates oxygen‐glucose deprivation/reoxygenation‐induced apoptosis and oxidative stress in HT22 neurons by targeting Brg1 to activate Nrf2/HO‐1 signalling
Author(s) -
Li Feng,
Liang Jing,
Tong Hua,
Zhu Shuai,
Tang Dongfang
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13265
Subject(s) - neuroprotection , oxidative stress , downregulation and upregulation , gene silencing , reactive oxygen species , apoptosis , ischemia , microrna , chemistry , reperfusion injury , microbiology and biotechnology , pharmacology , biology , medicine , biochemistry , gene
MicroRNAs (miRNAs) have emerged as critical regulators of neuronal survival during cerebral ischaemia/reperfusion injury. Accumulating evidence has shown that miR‐199a‐5p plays a crucial role in regulating apoptosis and survival in various cell types. However, whether miR‐199a is involved in regulating neuronal survival during cerebral ischaemia/reperfusion injury remains unknown. In this study, we aimed to explore the biological role of miR‐199a‐5p in regulating neuronal injury induced by oxygen‐glucose deprivation/reoxygenation (OGD/R), an in vitro cellular model of cerebral ischaemia and reperfusion injury. We found that miR‐199a‐5p expression was significantly altered in neurons in response to OGD/R treatment. Overexpression of miR‐199a‐5p facilitated OGD/R‐induced apoptosis and reactive oxygen species (ROS) production, whereas miR‐199a‐5p inhibition alleviated OGD/R‐induced apoptosis and ROS production. Notably, our results identified Brahma‐related gene 1 (Brg1) as a target gene of miR‐199a‐5p. Moreover, inhibition of miR‐199a‐5p promoted the activation of nuclear factor‐erythroid‐2‐related factor‐2 (Nrf2)/heme oxygenase‐1 (HO‐1) signalling via targeting Brg1. However, silencing of Brg1 markedly reversed the miR‐199a‐5p inhibition‐mediated neuroprotective effect. Taken together, our results suggest that downregulation of miR‐199a‐5p protects neurons from OGD/R‐induced neuronal injury through upregulating Brg1 to activate Nrf2/HO‐1 signalling. The miR‐199a‐5p/Brg1/Nrf2/HO‐1 regulation axis may play an important role in regulating neuronal survival during cerebral ischaemic/reperfusion injury in vivo.