Study Of MiR-23a Involved In Apoptosis In Mesenchymal Stem Cells And Myocardial Infarction

ObjectivesInvestigating the role of miR-23in the process of mesenchymal stem cells（MSCs） apoptosis stimulated by TNF-α as well as myocardial infarction. Andevaluating the therapeutic effects on myocardial infarction through transplantation ofmiR-23a overexpressed MSCs on related animal models.BackgroundMSCs can repair myocardial cell damage, which brings new sight on the therapyof myocardial infarction caused mainly by myocardial cell damage. However, forclinical application, there are still many problems to be solved, and the low survivalrate of transparented MSCs is the main obstacle. One possible reason for the lowsurvival rate is apoptosis induced by TNF-α, which is an important apoptosis factor invivo. Also, some MicroRNAs probably participate this process, such as miR-23a. Inorder to invetigate the role of miR-23a in the therapy of MSCs apoptosis andmyocardial infarction induced by TNF-α, we did the following work:Investigating the role of miR-23a in MSCs apoptosis induced by TNF-α on cellmodel in vitro, and further studying the mechanism.Evaluating the therapeutic effects of transplantation of miR-23a overexpressedMSCs on rat myocardial infarction model.Methods:(1)Detect the efficiency of TNF-α induced apoptosis by TUNEL assay and theTNF-α concentration dependency. (2)Analyze the expression level of miR-126，miR-23a，miR-125b in MSCs in thepresence of TNF-α or not.(3)Investigate the role of miR-23a in the process of apoptosis induced by TNF-αthrough knocking down or over expression of miR-23a in MSCs cell model in vitro.And investigate the role of caspase-7in the process at the mean while.(4)Evaluate the therapeutic effects of transplantation of miR-23a over expressedMSCs on rat myocardial infarction rat models by comparing left ventricular globalfunction and infracted tissue size of control MSCs transfected with GFP plasmid withtest MSCs transfected with miR-23a plasmid.Result:(1) TNF-α induce cell apoptosis in a concentration-dependent manner.Theexpression of miR-126,miR135b,miR-23a decreased significantly24hours afeter add10ng/ml TNF-α to mesenchymal stem cells.(2) Successfully established a high expression of miR-23a of bone marrowmesenchymal stem cell line.(3) Caspase-7is the target of miR23-a in TNF-α induce mesenchymal stem cellsapoptosis. The expression of caspase-7increased significantly in miR-23a knockdown cell line,but decreased significantly in high expression of miR-23a cell line.(4) Transplantation with high expression of miR-23a of mesenchymal stem cellsafter myocardial infarction myocardial injury has a protective effect.Conclusion:We proved that miR-23a plays a critical role in MSCs apoptosis induced by TNF-α through regulating the expression of caspase-7. miR-23a overexpressed MSCscan improve left ventricular global function and decrease the size of infarcted tissue.Our study provide new theory basis for alternative therapy for those MI patients whois not suitable for surgical treatment（CABG）.