title: NAMPT regulates senescence, proliferation, and migration of endothelial progenitor cells through the SIRT1 AS lncRNA/miR-22/SIRT1 pathway.
abstract: 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.
authors: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Guang-Feng
authors: GF
authors: Ming
authors: Department of Physiatry, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Kai
authors: K
authors: Wu
authors: Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Kai
authors: K
authors: Hu
authors: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors: Yao
authors: Y
authors: Chen
authors: Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China. Electronic address: admanoas@163.com.
authors: Jian
authors: J
authors: Xiao
mesh_terms: D000818:Animals; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D056564:Sirtuin 1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D035683:MicroRNAs; C574876:Mirn22 microRNA, mouse; D062085:RNA, Long Noncoding; C000619513:long non-coding RNA SIRT1 AS, mouse; D054409:Nicotinamide Phosphoribosyltransferase; D056564:Sirtuin 1
keywords: Endothelial progenitor cells; NAMPT; SIRT1; Senescence; lncRNA; miR-22