The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy.

The Expression of Tristetraprolin and Its Relationship with Urinary Proteins in Patients with Diabetic Nephropathy.
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糖尿病肾病患者三四脯氨酸的表达及其与尿蛋白的关系

DOI:
10.1371/journal.pone.0141471
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Liu Z
Liu Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu F;Guo J;Zhang Q;Liu D;Wen L;Yang Y;Yang L;Liu Z

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目的Tristetraprolin(TTP),又称锌指蛋白36,是一种RNA结合蛋白,对富含AU元件的mRNA表达具有重要调控作用。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2型糖尿病患者TTP水平与肾病相关的假设。方法87例2型糖尿病患者(61.3±9.6岁)和41例年龄、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。结果糖尿病患者血清和尿IL-6、IL-18水平显著高于对照组,而TTP水平显著低于对照组。此外,与无蛋白尿或微量白蛋白尿患者相比,有蛋白尿患者的血清和尿液IL-6和IL-18水平显著升高,而TTP水平显著降低。血清TTP与IL-6/IL-18呈显著相关(r =-0.572和-0.685,P < 0.05)。结论糖尿病临床蛋白尿患者尿及血清TTP水平降低,IL-6、IL-18水平升高。TTP表达的降低可能先于IL-6和IL-18的升高,TTP的降低可能比IL-6和IL-18更早地提供肾小球功能障碍的标志物。
Objective 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. Methods 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). Results 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). Conclusion 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.