NAMPT regulates senescence, proliferation, and migration of endothelial progenitor cells through the SIRT1 AS lncRNA/miR-22/SIRT1 pathway

作者：Ming, Guang-feng; Wu, Kai; Hu, Kai; Chen, Yao; Xiao, Jian^*

来源：Biochemical and Biophysical Research Communications, 2016, 478(3): 1382-1388.

DOI：10.1016/j.bbrc.2016.08.133

• NAMPT
• SIRT1
• lncRNA
• miR-22
• Endothelial progenitor cells
• Senescence

The importance of endothelial progenitor cells (EPCs) in cardiovascular diseases has been demonstrated by numerous studies. Previous studies have shown that Nicotinamide phosphoribosyltransferase (NAMPT) plays a role in EPC development by regulating Sirtuin 1 (SIRT1), but the specific mechanism has not yet been elucidated. After stimulating EPCs with NAMPT, expression of SIRT1 and SIRT1 antisense long non- coding RNA (AS lncRNA) was upregulated. Upon transfection of an SIRT1 AS lncRNA overexpression vector into EPCs, SIRT1 expression was upregulated. Upon transfection of a small interfering RNA (siRNA) that targets SIRT1 AS lncRNA along with NAMPT, SIRT1 AS lncRNA was downregulated and NAMPT- induced SIRT1 expression was reduced. We used software analyses and a dual- luciferase reporter assay to demonstrate that microRNA (miR)- 22 regulated SIRT1 and SIRT1 AS lncRNA. Our data suggest that SIRT1 AS lncRNA relieves miR-22-induced SIRT1 downregulation by competitively sponging miR-22. By measuring EPC senescence, proliferation, and migration, we found that NAMPT inhibited EPC senescence through an SIRT1 AS lncRNA/ miR-22/ SIRT1 pathway and promoted EPC proliferation and migration. These findings provide a new theoretical basis for the prevention and treatment of atherosclerosis (AS) and other cardiovascular diseases.

• 出版日期2016-9-23
• 单位中南大学