Chen Xiaoting, Wu Mian, Liang Nan, Lu Junxi, Qu Shen, Chen Haibing
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Endocrinology and Metabolism, Shanghai 10th People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Cell Dev Biol. 2021 Apr 1;9:636802. doi: 10.3389/fcell.2021.636802. eCollection 2021.
The relationship between thyroid hormones and serum urate is unclear. Our aim is to analyze the correlation between uric acid and thyroid hormones in gout patients and to explore the effect and mechanism of triiodothyronine on liver uric acid production. Eighty men patients with gout were selected to analyze the correlation between blood urate and thyroid function-related hormone levels. Stepwise multiple linear regression was used to analyze factors affecting blood urate in patients with gout. Levels of urate in serum, liver, and cell culture supernatant were measured after triiodothyronine treatment. Purine levels (adenine, guanine, and hypoxanthine) were also measured. Expression levels of Period2 and nucleotide metabolism enzymes were analyzed after triiodothyronine treatment and Period2-shRNA lentivirus transduction. Chromatin immunoprecipitation was used to analyze the effects of triiodothyronine and thyroid hormone receptor-β on Period2 expression. The results showed that in patients FT3 influenced the serum urate level. Furthermore, urate level increased in mouse liver and cell culture supernatant following treatment with triiodothyronine. Purine levels in mouse liver increased, accompanied by upregulation of enzymes involved in nucleotide metabolism. These phenomena were reversed in Period2 knockout mice. Triiodothyronine promoted the binding of thyroid hormone receptor-β to the Period2 promoter and subsequent transcription of Period2. Triiodothyronine also enhanced nuclear expression of Sirt1, which synergistically enhanced Period2 expression. The study demonstrated that triiodothyronine is independently positively correlated with serum urate and liver uric acid production through Period2, providing novel insights into the purine metabolism underlying hyperuricemia/gout pathophysiology.
甲状腺激素与血清尿酸之间的关系尚不清楚。我们的目的是分析痛风患者尿酸与甲状腺激素之间的相关性，并探讨三碘甲状腺原氨酸对肝脏尿酸生成的影响及机制。选取80例男性痛风患者，分析血尿酸与甲状腺功能相关激素水平之间的相关性。采用逐步多元线性回归分析影响痛风患者血尿酸的因素。三碘甲状腺原氨酸处理后，检测血清、肝脏和细胞培养上清液中的尿酸水平。同时检测嘌呤水平（腺嘌呤、鸟嘌呤和次黄嘌呤）。三碘甲状腺原氨酸处理及Period2-shRNA慢病毒转导后，分析Period2和核苷酸代谢酶的表达水平。采用染色质免疫沉淀法分析三碘甲状腺原氨酸和甲状腺激素受体-β对Period2表达的影响。结果显示，在患者中FT3影响血清尿酸水平。此外，三碘甲状腺原氨酸处理后，小鼠肝脏和细胞培养上清液中的尿酸水平升高。小鼠肝脏中的嘌呤水平升高，同时参与核苷酸代谢的酶上调。这些现象在Period2基因敲除小鼠中得到逆转。三碘甲状腺原氨酸促进甲状腺激素受体-β与Period2启动子的结合及随后Period2的转录。三碘甲状腺原氨酸还增强了Sirt1的核表达，协同增强了Period2的表达。该研究表明，三碘甲状腺原氨酸通过Period2与血清尿酸和肝脏尿酸生成独立正相关，为高尿酸血症/痛风病理生理学的嘌呤代谢提供了新的见解。
