Liu Fengxun, Guo Jia, Zhang Qian, Liu Dongwei, Wen Lu, Yang Yang, Yang Liu, Liu Zhangsuo
Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China; Nephropathy Research Institutes of Zhengzhou University, Zhengzhou, People's Republic of China; Key-Disciplines Laboratory Clinical-Medicine Henan, Zhengzhou, People's Republic of China.
PLoS One. 2015 Oct 30;10(10):e0141471. doi: 10.1371/journal.pone.0141471. eCollection 2015.
Tristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes.
Eighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR).
Serum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05).
These results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.
锌指蛋白36也被称为Tristetraprolin（TTP），是一种RNA结合蛋白，在调节含有富含AU元件的mRNA表达中发挥重要作用。我们推测TTP可能调节糖尿病患者白细胞介素（IL）-6和IL-18的表达。本研究旨在验证TTP水平与2型糖尿病患者肾病相关的假说。
纳入87例已确诊为2型糖尿病的患者（年龄61.3±9.6岁）以及41例年龄和性别相匹配的健康对照者。根据尿白蛋白/肌酐排泄率（ACR），将糖尿病患者分为无蛋白尿组、微量白蛋白尿组和临床蛋白尿组。
与对照组相比，糖尿病患者血清和尿液中IL-6和IL-18水平显著升高，但TTP水平显著降低。此外，与无蛋白尿或微量白蛋白尿的患者相比，蛋白尿患者血清和尿液中IL-6和IL-18水平显著更高，但TTP水平显著更低。血清TTP与IL-6/IL-18之间存在显著相关性（相关系数分别为-0.572和-0.685，P<0.05）。
这些结果表明，伴有临床蛋白尿的糖尿病患者尿液和血清中TTP水平降低，IL-6和IL-18水平升高。TTP表达降低可能发生在IL-6和IL-18升高之前，与IL-6和IL-18相比，TTP降低可能是肾小球功能障碍的更早标志物。
