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Research Paper|Volume 13, Issue 8|pp 11877—11888

Overexpression of microRNA-202-3p in bone marrow mesenchymal stem cells improves cerebral ischemia-reperfusion injury by promoting angiogenesis and inhibiting inflammation

Guohua Yu1, Weiming Sun1, Wansong Wang1, Changhao Le1, Dehuan Liang1, Lang Shuai1
  • 1Department of Rehabilitation, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
Received: June 19, 2020Accepted: February 27, 2021Published: April 23, 2021
https://doi.org/10.18632/aging.202889

Copyright: © 2021 Yu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Cerebral ischemia-reperfusion injury (CIRI) can cause brain tissue inflammation, neuronal degeneration, and apoptosis. There is increasing evidence that microRNAs (miRNA) exert neuroprotective effects by regulating the inflammatory process during cerebral ischemia-reperfusion injury. Additionally, it is increasingly acknowledged that neuroinflammation is regulated by Toll-like receptor 4 (TLR4). However, it is unclear whether miRNA can exert its neuroprotective effects by regulating TLR4-mediated inflammation.

Methods: The effects of BMSCs over-expressing miR-202-3p on CIRI, angiogenesis in midbrain tissue, and the release of inflammatory factors (IFs) in the serum were measured using in vivo rat models. We also used SH-SY5Y cells to establish an ischemia-reperfusion in vitro cell model. The interaction between miR-202-3p and TLR4 was analyzed by overexpressing miR-202-3p and knocking down TLR4. Knockdown of TLR4 was performed using siRNA.

Results: Overexpression of miR-202-3p in BMSCs could significantly improve brain function and reduce brain damage. Simultaneously, miR-202-3p could significantly promote angiogenesis, increase the expression of vWF and VEGF, and reduce the expression of IFs. When the expression of TLR4 was significantly reduced in SH-SY5Y cells, the expression of IFs increased. Therefore, miRNA-202-3p may interact with TLR4 to modulate inflammation.

Conclusion: Our data indicated that miR-202-3p potentially exerts its neuroprotective effects and protects against CIRI by regulating TLR4-mediated inflammation.