Improvement of cardiac function by mesenchymal stem cells derived extracellular vesicles through targeting miR-497/Smad7 axis

Abstract

Background: The extracellular vesicles (EVs) secreted by bone marrow mesenchymal stromal cells (MSCs) have the ability to improve Myocardial infarction (MI). Some microRNAs (miRNAs) including miR-497 and related target genes have been proved to be closely linked with heart diseases. However, EVs could regulate MI process through miR-497, and the mechanisms have not been fully reported. Methods: Ligation of left anterior descending artery was performed to established MI animals model. Hypoxia cell model was established through lowering the level of oxygen. The cell invasion, migration, and proliferation were measured using tanswell, wound heating, and MTT assays. HE, Masson trichrome, and Sirius Red staining were used to investigate the morphological changes. Results: Overexpression of miR-497 reversed the promotion of cell migration, invasion, and proliferation caused by EVs. The improvement of cardiac function induced by EVs could also be reversed by overexpression of miR-497. Direct binding site between Smad7 and miR-497 was identified. Knockdown of Smad7 reversed the improvement of cardiac function induced by EVs. Conclusions: We found that EVs isolated from MSCs might improve the cardiac injury caused by MI through targeting miR497/Smad7. This study provides novel potential therapeutic thought for the prevention and treatment of MI through targeting miR-497/Smad7.

Senescence and SASP Are Potential Therapeutic Targets for Ischemic Stroke

“…SIRT1 alleviates senescence by activating cell division and inhibits senescence by deacetylation of p53. In addition, mesenchymal stem cell (MSC) therapy is another therapeutic avenue for alleviating the premature senescence associated with IR injury [ 107 , 108 , 109 ]. MSCs secret various soluble factors and exosomes with immunomodulatory properties, which can inhibit SASP and attenuate senescence [ 108 , 110 , 111 ].…”

“…In addition, mesenchymal stem cell (MSC) therapy is another therapeutic avenue for alleviating the premature senescence associated with IR injury [ 107 , 108 , 109 ]. MSCs secret various soluble factors and exosomes with immunomodulatory properties, which can inhibit SASP and attenuate senescence [ 108 , 110 , 111 ]. Recently, Xiao et al demonstrated that MSC-derived extra-cellular vesicles stimulate angiogenesis and attenuate endothelial senescence [ 112 ].…”

Cellular senescence in ischemia/reperfusion injury

“…On the other hand, MSCs can secret extracellular vesicles (EVs) to inhibit the generation of SASP in senescent cells [ 129 , 130 ]. For instance, cell-cycle arrest of myocardiocytes after MI can be alleviated by MSC-EVs carrying miR-150-5p via downregulation of TXNIP [ 131 , 132 ], or by MSC-EVs targeting miR-497/Smad7/TGF-β pathway [ 133 ]. Yu et al also found that EVs carrying mi-202-3p could protect neurons from IR injury via downregulating TLR4-mediated inflammation response [ 124 ].…”