NAMPT regulates senescence, proliferation, and migration of endothelial progenitor cells through the SIRT1 AS lncRNA/miR-22/SIRT1 pathway
NAMPT regulates senescence, proliferation, and migration of endothelial progenitor cells through the SIRT1 AS lncRNA/miR-22/SIRT1 pathway
复制标题
NAMPT 通过 SIRT1 AS lncRNA/miR-22/SIRT1 通路调节内皮祖细胞的衰老、增殖和迁移
DOI：
10.1016/j.bbrc.2016.08.133
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发表时间：
2016-09-23
影响因子：
3.1
通讯作者：
Xiao, Jian
中科院分区：
文献类型：
--
作者：
Ming, Guang-feng;Wu, Kai;Xiao, Jian
大量研究表明内皮祖细胞在心血管疾病中的重要性。已有研究表明，烟酰胺磷酸核糖转移酶(NAMPT)通过调节Sirtuin 1(SIRT1)在EPC的发生发展中起作用，但其具体机制尚未阐明。NAMPT刺激内皮祖细胞后，SIRT1和SIRT1反义长非编码RNA(AS LncRNA)的表达上调。将SIRT1作为lncRNA过表达载体导入内皮祖细胞后，SIRT1表达上调。将靶向SIRT1的小干扰RNA(SiRNA)与NAMPT共同作用后，SIRT1作为LncRNA的表达下调，NAMPT诱导的SIRT1表达减少。我们使用软件分析和双荧光素酶报告实验证明，microRNA(MiR)-22调控SIRT1和SIRT1作为lncRNA。我们的数据表明，SIRT1作为lncRNA通过竞争性地吞噬miR-22来缓解miR-22诱导的SIRT1下调。通过检测EPC的衰老、增殖和迁移，我们发现NAMPT通过SIRT1途径抑制EPC的衰老，促进EPC的增殖和迁移。这些发现为防治动脉粥样硬化(AS)等心血管疾病提供了新的理论依据。(C)2016 Elsevier Inc.保留所有权利。
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. (c) 2016 Elsevier Inc. All rights reserved.