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

Abstract

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.

• Authors: Yin Du, Xiaozhen Ma, Lei Ma, Siyuan Li, Juan Zheng, Junlin Lv, Long Cui, Jianrui Lv
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 47 Issue 4 Pg. 561-570 (04 2020) ISSN: 1440-1681 [Electronic] Australia
• PMID: 31868937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 John Wiley & Sons Australia, Ltd.

Chemical References

• MicroRNAs
• Mirn148 microRNA, mouse
• NF-E2-Related Factor 2
• Reactive Oxygen Species
• Sestrins
• Glucose
• Oxygen

Topics

• Animals
• Apoptosis (genetics)
• Cell Line
• Cell Survival (genetics)
• Glucose (metabolism)
• Hippocampus (cytology)
• Mice
• MicroRNAs (genetics)
• NF-E2-Related Factor 2 (metabolism)
• Neurons (cytology, metabolism)
• Oxidative Stress (genetics)
• Oxygen (metabolism)
• Reactive Oxygen Species (metabolism)
• Sestrins (metabolism)
• Signal Transduction (genetics)