1476-PUB: The Stimulation of High Glucose Can Downregulate Expression of miR-223-3p in HUVECs, Which May Undergo Endothelial–Myofibroblast Transition

Abstract

The early changes in renal glomeruli are crux for the development of glomerulosclerosis and nephron dropout in diabetic kidney disease (DKD) . Many studies have focused on the changes of the dysfunction of glomerular podocytes, the study of glomerular endothelial cells (GECs) are not completely understood. Human umbilical vein endothelial cells (HUVECs) are considered the classic model of endothelial cells (ECs) . The stimuliation of high glucose would induce the stress or injury of ECs. In our previous study, with the development of DKD, the the expression of miR-223-3p was significantly decreased in patients’ peripheral plasma, and bioinformatics methods predicted IL6ST as the target gene of miR-223-3p. We also proved that miR-223-3p target IL6ST and down-regulate its expression in 293T cells by using dual-luciferase reporter assay system.So the down-regulation of miR-223-3p could be viewed which induced by high glucose 24 hours in HUVECs and its target gene IL6ST significantly increased. After using high glucose stimulate the HUVECs, the proliferation and migration of HUVECs decreased, the qPCR study suggest that the expression of miR-223-3p significantly decreased, the endothelial jnjury factors (aVEGF, ET1) increased, and the fibrosis factor (αSMA, FN1) also increased. When up-regulate the expression of miR-223-3p in HUVECs by using miR-223-3p-mimic, the expression of IL6ST is down-regulated.The HUVECs may undergo endothelial-myofibroblast transition (EndoMT) after high glucose stimulation, and this process may be one of the cause of DKD glomerulosclerosis. Disclosure J.Zhang: None. P.Tang: None. L.Zhang: None. P.Li: None. Funding Financial Support: National Natural Science Foundation of China (81960156) , and Health Science and Technology Program of Yunnan Province[2019FE001 (-040) ]