Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Institute of EndocrineRuijin Hospital, Shanghai Jiao-Tong University School of Medicine, China.
Division of Endocrinology and Metabolism, Department of Internal Medicine, RenJi Hospital, Shanghai Jiao-Tong University School of Medicine, Pudong, Shanghai, China.
J Endocrinol. 2020 Aug;246(2):161-173. doi: 10.1530/JOE-19-0501.
SIRT1, a class III histone/protein deacetylase (HDAC), has been associated with autoimmune diseases. There is a paucity of data about the role of SIRT1 in Graves' disease. The aim of this study was to investigate the role of SIRT1 in the pathogenesis of GD. Here, we showed that SIRT1 expression and activity were significantly decreased in GD patients compared with healthy controls. The NF-κB pathway was activated in the peripheral blood of GD patients. The reduced SIRT1 levels correlated strongly with clinical parameters. In euthyroid patients, SIRT1 expression was markedly upregulated and NF-κB downstream target gene expression was significantly reduced. SIRT1 inhibited the NF-κB pathway activity by deacetylating P65. These results demonstrate that reduced SIRT1 expression and activity contribute to the activation of the NF-κB pathway and may be involved in the pathogenesis of GD.
SIRT1 是一种 III 类组蛋白/蛋白质去乙酰化酶（HDAC），与自身免疫性疾病有关。关于 SIRT1 在格雷夫斯病中的作用的数据很少。本研究旨在探讨 SIRT1 在 GD 发病机制中的作用。在这里，我们表明与健康对照组相比，GD 患者的 SIRT1 表达和活性显著降低。NF-κB 途径在 GD 患者的外周血中被激活。减少的 SIRT1 水平与临床参数密切相关。在甲状腺功能正常的患者中，SIRT1 的表达明显上调，NF-κB 下游靶基因的表达显著降低。SIRT1 通过去乙酰化 P65 抑制 NF-κB 途径的活性。这些结果表明，SIRT1 表达和活性的降低导致 NF-κB 途径的激活，可能与 GD 的发病机制有关。
