Abstract
ObjectiveTristetraprolin (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.MethodsEighty-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).ResultsSerum 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).ConclusionThese 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.
Highlights
Diabetes mellitus has become the leading cause of chronic renal failure in developed countries and is increasing as a cause of morbidity and mortality worldwide [1]
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
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
Summary
Diabetes mellitus has become the leading cause of chronic renal failure in developed countries and is increasing as a cause of morbidity and mortality worldwide [1]. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus and has become the principal cause of end-stage renal failure. About 31% -40% of diabetes mellitus patients develop diabetic nephropathy, which poses a serious health threat [2]. The serum levels of IL-6, which is directly associated with early glomerular structural abnormalities, have been shown to be substantially higher in type 2 diabetes mellitus (T2DM) patients with DN than in T2DM patients without renal disease. Given the association of IL-18 with multiple related inflammatory diseases, the levels of IL-18 might be useful as an early marker of renal dysfunction in patients with T2DM [3,4]
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