MiR-126 Exert Protection Of Homing Of Endothelial Progenitor Cells In DM Background

Purpose: The endothelium-regenerative ability of EPCs is impaired in patients with type-2 diabetes mellitus(DM). Micro RNAs(mi RNAs) are key regulators of diverse cellular processes including angiogenesis. Down-regulated expression of CXCR4 in EPCs and the subsequent SDF-1?/CXCR4 signal transcriptional disorder are currently recognized as a major mechanism responsible for impaired EPCs homing in diabetic patients. Our previous study showed that mi R-126 was aberrantly down-regulated in the EPCs in DM patients, and downregulated mi R-126 in type II diabetes mellitus(DM) patients causes EPCs dysfunction. However, we still want to know the relationship between mi R-126 expression in EPCs with high glucose(HG), and its metabolites, such as advanced glycation end products(AGEs), reactive oxygen species(ROS) and inflammation factors, and the underlying mechanism of mi R-126 in the process of mobilization and immigration of EPCs.Methods: In the present study, we explored the different concentration of high blood glucose and AGEs on EPCs' proliferation. Then we explored the mi R-126 expression by RT-PCR under HG and AGEs, and the mechanisms by which AGEs regulate mi R-126 expression. We also explored the effects and mechanisms of mi R-126 on CXCR4 expression and SDF-1a-induced EPCs migration to clarify mi R-126's effect on the regulation of SDF-1a/CXCR4-induced EPCs mobilization.Results: We found high glucose increased ROS, IL-6 and TNF-? generation in EPCs during the initial 24 h, while it decreased mi R-126 expression after 48 h. Also we found the detrimental effects of AGEs not only limited to increase ROS, IL-6 and TNF-?, but also to decrease mi R-126 expression concentration-dependently. Yet, over expression of mi R-126 may reduce the inflammation and ROS induced by HG and AGEs and inhibition of mi R-126 may promote the inflammation and ROS caused by HG and AGEs. AGEs regulate mi R-126 expression through PI3K/Akt signals. The migration number of EPCs is dependent on SDF-1?. Over expression of mi R-126 may increase the expression of CXCR4 and the migration ability of EPCs induced by SDF-1?; inhibition of mi R-126 may decrease the expression of CXCR4 and the migration ability of EPCs induced by SDF-1?. Mi R-126 may influence SDF-1?/CXCR4 through PI3K/Akt/e NOS and VEGF signals.Conclusions: In conclusion, hyperglycemia and AGEs decreased mi R-126 expression in EPCs and caused EPCs dysfunction. Mi R-126 may exert protection on SDF-1?/CXCR4 induced EPCs homing through PI3K/Akt/e NOS and VEGF signals. Mi R-126 may be one of the important targets in EPCs in diabetes background.