The aim of our work was to test whether thymosin beta 4 protected endothelial progenitor cells against apoptosis induced by advanced glycation endproducts and investigate the underlying mechanism. Treatment with thymosin beta 4 or transfection with microRNA-34a inhibitor enhanced cell viability, reduced apoptosis, abated oxidative stress, and attenuated mitochondrial dysfunction in endothelial progenitor cells exposed to advanced glycation endproducts. Incubation with advanced glycation endproducts led to increased levels of microRNA-34a, which was attenuated by treatment with thymosin beta 4. Transfection with microRNA-34a reversed the beneficial effect of thymosin beta 4 against injuries induced by advanced glycation endproducts. The microRNA-34a could directly bind to the 3'UTRs of the mRNA of B-cell lymphoma 2, and thymosin beta 4 treatment upregulated B-cell lymphoma 2 expression in endothelial progenitor cells exposed to advanced glycation endproducts. More importantly, knockdown of B-cell lymphoma 2 abolished the protection of thymosin beta 4 and microRNA-34a inhibitor against advanced glycation endproducts. In conclusion, inhibition of microRNA-34a mediated protection of thymosin beta 4 in endothelial progenitor cells against advanced glycation endproducts by targeting B-cell lymphoma 2, which was helpful for understanding the therapeutic potential of thymosin beta 4 for diabetic patients.
Keywords: advanced glycation endproducts; bcl-2; cellules souches endothéliales; endothelial progenitor cells; microRNA-34a; produits finaux de glycation avancée; thymosin beta 4; thymosine bêta 4.