miRNA-181a over-expression in mesenchymal stem cell-derived exosomes influenced inflammatory response after myocardial ischemia-reperfusion injury.
AIMS
The inflammation modulation effects of mesenchymal stromal cell-derived exosomes (MSC-EXO) are well established. We aimed to explore the mechanism behind the inflammatory responses of numerous exosomal cargo molecules that have been neglected in molecular biology research, and to develop an exosomal cargo delivery system that can exert a stronger therapeutic effect on myocardial ischemia-reperfusion (I/R) injury.


MAIN METHODS
Computational approaches were used to identify key exosomal miRNAs and their downstream mRNAs that are expressed in the inflammatory response. Direct interactions between miRNA-181a and the c-Fos mRNA complex were confirmed by luciferase reporter assay. MSC-EXO carrying miRNA-181a-overexpressing lentiviruses were intramyocardially injected into a mouse model of myocardial I/R injury. I/R progression was evaluated through echocardiography and immunofluorescence microscopy.


KEY FINDINGS
miRNA-181a provided substantial coverage against a host of immune-related genes through the miRNA-mRNA network. miRNA-181a delivery by MSC-EXO combined the immune-suppressing effect of miRNA-181a and the cell targeting capability of MSC-EXO to exert a stronger therapeutic effect on myocardium I/R injury.


SIGNIFICANCE
We showed the potential of MSC-EXO as a tool for the specific delivery of small RNAs in vivo. This study shed new light on the potential application of miRNA-181a-overexpressing MSC-EXO as a therapeutic strategy for myocardial I/R injury.
['Wei|Zilun|Z|', 'Qiao|Shuaihua|S|', 'Zhao|Jinxuan|J|', 'Liu|Yihai|Y|', 'Li|Qiaoling|Q|', 'Wei|Zhonghai|Z|', 'Dai|Qing|Q|', 'Kang|Lina|L|', 'Xu|Biao|B|']
D000818:Animals D002465:Cell Movement D049109:Cell Proliferation D036101:Cord Blood Stem Cell Transplantation D055354:Exosomes D006801:Humans D007249:Inflammation D008297:Male D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D051379:Mice D008810:Mice, Inbred C57BL D035683:MicroRNAs D015428:Myocardial Reperfusion Injury D015427:Reperfusion Injury
miRNA-181a Inflammation C-Fos Bioinformatics Myocardial infarction Regulatory T cell