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

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.

• Authors: Guohua Yu, Weiming Sun, Wansong Wang, Changhao Le, Dehuan Liang, Lang Shuai
• Journal: Aging (Aging (Albany NY)) Vol. 13 Issue 8 Pg. 11877-11888 (04 23 2021) ISSN: 1945-4589 [Electronic] United States
• PMID: 33893248 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• MIRN202 microRNA, human
• MicroRNAs
• TLR4 protein, human
• Tlr4 protein, rat
• Toll-Like Receptor 4

Topics

• Animals
• Apoptosis (genetics)
• Brain Ischemia (blood, complications, immunology, therapy)
• Cell Line, Tumor
• Disease Models, Animal
• Gene Knockdown Techniques
• Genetic Vectors (genetics)
• Humans
• Inflammation (blood, genetics, immunology)
• Inflammation Mediators (blood, metabolism)
• Lentivirus (genetics)
• Male
• Mesencephalon (blood supply, immunology, pathology)
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (metabolism)
• MicroRNAs (genetics, metabolism)
• Neovascularization, Physiologic (genetics)
• Primary Cell Culture
• Rats
• Reperfusion Injury (blood, immunology, pathology, prevention & control)
• Toll-Like Receptor 4 (genetics)
• Transfection