Inhibition of microRNA-148b-3p alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in HT22 hippocampal neuron via reinforcing Sestrin2/Nrf2 signalling

Du，Yin1; Ma，Xiaozhen2; Ma，Lei1; Li，Siyuan1; Zheng，Juan1; Lv，Junlin1; Cui，Long3; Lv，Jianrui1

2020-04-01

10.1111/1440-1681.13231

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY   影响因子和分区

0305-1870

1440-1681

MicroRNAs (miRNAs) have emerged as crucial regulators of neuronal injury during cerebral ischaemia/reperfusion injury. Various miRNAs are dysregulated during this pathological process; however, the precise role of these miRNAs in regulating neuronal injury remains largely unknown. In the current study, we explored the potential function of microRNA-148b-3p (miR-148b-3p) in regulating neuronal injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro, a cellular model for mimicking cerebral ischaemia/reperfusion injury. We found that miR-148b-3p expression was significantly decreased in neurons in response to OGD/R exposure. Importantly, miR-148b-3p overexpression decreased cell viability and exacerbated apoptosis and reactive oxygen species (ROS) production in OGD/R-exposed neurons. By contrast, miR-148b-3p inhibition improved cell viability and decreased apoptosis and ROS production in OGD/R-exposed neurons. Notably, Sestrin2, a cytoprotective gene, was identified as a miR-148b-3p target gene. miR-148b-3p inhibition markedly increased Sestrin2 expression as well as the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) antioxidant signalling. Moreover, silencing of Sestrin2 or Nrf2 significantly reversed the miR-148-3p-inhibition-mediated protective effect in OGD/R-injured neurons. Overall, these results demonstrate that miR-148b-3p inhibition protects neurons from OGD/R-induced apoptosis and ROS production through reinforcing Nrf2 antioxidant signalling via upregulation of Sestrin2. Our study indicates that the miR-148b-3p/Sestrin2/Nrf2 axis plays an important role in regulating neuronal injury and may serve as a potential therapeutic target for providing neuroprotection during cerebral ischaemia/reperfusion injury.

cerebral ischaemia/reperfusion injury miR-148b-3p Nrf2 Sestrin2

SCI

英语

其他

Key Research & Development Project of Shaanxi Province[2018SF-010]

Pharmacology & Pharmacy ; Physiology

Pharmacology & Pharmacy ; Physiology

WOS:000508165300001

WILEY

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85078616061

Scopus

1.Department of Anesthesiology,The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an,China
2.Department of Physiology,Shaanxi University of Chinese Medicine,Xianyang City,China
3.Department of Otolaryngology,Southern University of Science and Technology Hospital,Shenzhen,China

Du，Yin,Ma，Xiaozhen,Ma，Lei,et al. Inhibition of microRNA-148b-3p alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in HT22 hippocampal neuron via reinforcing Sestrin2/Nrf2 signalling[J]. CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY,2020,47(4):561-570.

Du，Yin.,Ma，Xiaozhen.,Ma，Lei.,Li，Siyuan.,Zheng，Juan.,...&Lv，Jianrui.(2020).Inhibition of microRNA-148b-3p alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in HT22 hippocampal neuron via reinforcing Sestrin2/Nrf2 signalling.CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY,47(4),561-570.

Du，Yin,et al."Inhibition of microRNA-148b-3p alleviates oxygen-glucose deprivation/reoxygenation-induced apoptosis and oxidative stress in HT22 hippocampal neuron via reinforcing Sestrin2/Nrf2 signalling".CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 47.4(2020):561-570.