白藜芦醇通过SIRT1介导对VEGF/VEGFR2信号传导的抑制及其与脉络膜新生血管形成的相关性。
SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization.
作者信息
Zhang Huiming, He Shikun, Spee Christine, Ishikawa Keijiro, Hinton David R
机构信息
Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China; Departments of Pathology, Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Departments of Pathology, Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
出版信息
Cytokine. 2015 Dec;76(2):549-552. doi: 10.1016/j.cyto.2015.06.019. Epub 2015 Jul 11.
SIRT1, a NAD(+) -dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α/VEGF/VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV.
SIRT1是一种依赖烟酰胺腺嘌呤二核苷酸（NAD(+)）的组蛋白脱乙酰酶，已被证明是血管生成的关键调节因子。本研究旨在确定白藜芦醇（RSV，一种SIRT1激活剂）对血管内皮生长因子受体2（VEGFR2）信号通路的影响，并确定其与脉络膜新生血管（CNV）的相关性，CNV是年龄相关性黄斑变性的致盲并发症。蛋白质免疫印迹法和酶联免疫吸附测定法表明，RSV通过SIRT1抑制人视网膜色素上皮（hRPE）细胞中由氯化钴（CoCl2）诱导的缺氧诱导因子（HIF）-1α积累和VEGF分泌。此外，RSV通过SIRT1下调内皮细胞中由VEGF诱导的VEGFR2磷酸化和激活。因此，RSV对HIF-1α/VEGF/VEGFR2信号轴的抑制作用至少部分是通过SIRT1介导的。结果表明，靶向SIRT1可能对CNV的治疗具有潜在的治疗价值。
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