Abstract
Early brain injury (EBI) is a major cause of adverse outcomes following subarachnoid hemorrhage (SAH). There is evidence that mesenchymal stem cells (MSCs) - derived exosomes are involved in the repair of SAH. Exosomes were extracted from human umbilical cord mesenchymal stem cells (hubMSCs) and identified. OxyHb treated PC12 cells were transfected with exosomes alone or together with miR-26b-5p inhibitor. Hub-MSCs derived exosomes promote cell proliferation, inhibit apoptosis and reduce inflammatory mediator expression. Transfection of miR-26b-5p inhibitor abolished the promoting effect of exosomes on the proliferation of PC12 cells, as well as the inhibitory effect on cell apoptosis. In addition, methionine adenosyltransferase II alpha (MAT2A) was one target gene of miR-26b-5p. OxyHb treated PC12 cells were transfected with exosomes alone or together with pcDNA-MAT2A and observed that the promoting effect of exosomes on PC12 cell proliferation was abolished by pcDNA-MAT2A, which was the same as the effect of miR-26b-5p inhibitor. OxyHb treated PC12 cells incubated with exosomes were transfected with miR-26b-5p inhibitor alone or together with si-MAT2A, respectively, and it was observed that exosomes decreased the phosphorylation levels of p38 MAPK and STAT3 proteins, inhibited cell apoptosis and inflammatory mediator expression, and miR-26b-5p inhibitor abrogated the effects of exosomes, while transfection of si-MAT2A reversed the effects of miR-26b-5p inhibitor. Moreover, injection of miR-26b-5p inhibitor resulted in increased MAT2A and pathway protein expression, increased inflammatory mediators, and aggravated neurological symptoms in the brain tissues of SAH rats.
Exosomes from Bone Marrow Mesenchymal Stem Cells Can Alleviate Early Brain Injury After Subarachnoid Hemorrhage Through miRNA129-5p-HMGB1 Pathway
