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. 2020 Jun;47(6):1020-1029.
doi: 10.1111/1440-1681.13265. Epub 2020 Feb 10.

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

Feng Li  1 , Jing Liang  2 , Hua Tong  1 , Shuai Zhu  1 , Dongfang Tang  3
Affiliations

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

Feng Li et al. Clin Exp Pharmacol Physiol. 2020 Jun.

Abstract

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.

Keywords: Brahma-related gene-1; heme oxygenase-1; miR-199a-5p; nuclear factor-erythroid-2-related factor-2.

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References

REFERENCES

    1. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870-947.
    1. Krause GS, White BC, Aust SD, Nayini NR, Kumar K. Brain cell death following ischemia and reperfusion: a proposed biochemical sequence. Crit Care Med. 1988;16(7):714-726.
    1. Wang X, Lo EH. Triggers and mediators of hemorrhagic transformation in cerebral ischemia. Mol Neurobiol. 2003;28(3):229-244.
    1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-297.
    1. Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14(8):535-548.

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