The Expression Of Tristetraprolin In Patients With Diabetic Nephropathy And Its Relationship With Urinary Protein

BackgroundDiabetic nephropathy is one of the most common microvascular complicationsof diabetes in the United States and Europe.It has already become the major cause ofend-stage renal disease. According to some reprots, the number of diabetic patients inChina was more than90million. About31%-40%of diabetic patients maydevelopped to diabetic nephropathy. In the pathogenesis of diabetic nephropathy,inflammation is increasingly important. Renal intrinsic cells under pathologicalconditions could product a variety of inflammatory cytokines：TNF-α、IL-18、IL-6、NO and so on. These inflammatory factors interaction could lead the effect ofinflammation expanding.Partial factors could cause inflammation cascade reactionthrough paracrine and autocrine manner. so, the research of the incidence and theregulation.Reports that inflammation in diabetic nephropathy is very important andactivated mesangial cells have the ability to secrete interleukin-18.In theinflammatory reactions, IL-18is an important inflammatory cytokines and play a key role in the inflammatory cascade,IL-18could be considered as one of the early renaldamage marks of diabetic nephropathy.But there is still need further confirmed byclinical data. Reports have found that Tristetraprolin (TTP) was the prototype memberof the zinc finger protein (ZFP36) RNA binding proteins in CCCH-type zinc fingerfamily,and TTP can combined with mRNA3’UTR region AU-rich region, and thusregulate the expression of related proteins.TTP could degraded many inflammatorycytokines such as IL6, IL18and other inflammatory cytokines and they could becombined with the TTP. Researchs found that there were micro-inflammatory state indiabetic nephropathy.We guess there may be abnormal expression of TTP in patientswith diabetic nephropathy,and trying to understand the relationship between theexpression of TTP and IL18in diabetic nephropathy.The expression of TTP and itsrelationship with urinary protein in diabetic nephropathy was observed.ObjectiveTo study the expression trends of TTP and IL-18in blood and urine specimensof diabetic nephropathy and the relationship with urinary protein was detected toexplore the possibility of TTP as early renal damage biomarkers in diabeticnephropathy.Methods128cases of experimental subjects was select from the First Affiliated Hospitalof Zhengzhou University, January2013to December2013. Normal group:41caseswas collected in Medical Department; DM group:33cases was collected inEndocrinology;the rrest of subjects were collected in Nephrology. All subjects include65cases of male,63cases of female, the patient’s age was (60.7±10.9) years old.Detailed groups as follows:1.Control subjects（41cases）.2. T2DM Normoalbumiuriagroup （UAER＜30mg/24h,33cases）3. T2DM Microalbuminuria group（30mg/24h≤UAER<300mg/24h,29cases）4.（Clinical proteinuria group）（T2DMMacroalbuminuria,UAER≥300mg/24h,25cases）. Normal group was confirmed byphysical examination and laboratory tests, patients with diabetes and diabetic nephropathy group were diagnosed with type2diabetes, Fasting blood glucosegreater than7.0mmol/L,2-hour postprandial blood glucose greater than11.1mmol/L, no acute complications, with or without proteinuria. The gender/age/renal functionof patients in each group showed no significant difference between the two groups.Blood and urine samples of patients were detected by PCR and ELISA. Operationswere strict according to the instructions and test processes.ResultsThis study included128cases,65cases were male and63female, mean age(60.7±10.9) years old. Normal control group, diabetic group, microalbuminuriaand macroalbuminuria group UAER group were8.11±2.46mg/24h,9.18±2.67mg/24h,96.53±42.17mg/24h and601.42±133.29mg/24h. Urineelectrophoresis showed that TTP decreased with urinary protein increased in everygroups. pairwise comparisons showed proteinuria and microalbuminuria group wassignificantly lower than that in diabetic group and normal control group (P <0.05),while a large number of proteins no significant difference (P>0.05) between the twogroups with urinary microalbuminuria group. Further test patients urine samples byELISA showed Tristetraprolin in microalbuminuria and macroalbuminuria were148.47±20.33pg/ml and68.61±17.49pg/ml, significantly lower than thecontrol group (244.19±18.37pg/ml) and DM group (160.03±19.41pg/ml).Blood samples from the same period of the ELISA assay Tristetraprolin,consistent with the results of the urine specimen. Compared to normal control group(284.77±20.61pg/ml) and simple diabetic patients (196.14±17.11pg/ml),Tristetraprolin in microalbuminuria and proteinuria in patients with alarge plasma levels were lower:140.53±19.22bpg/ml and81.34±16.51pg/ml,the difference was statistically significant (P>0.05).To further explore therelationship between Tristetraprolin and urinary protein, we both correlation analysisshowed that patients with diabetic nephropathy Tristetraprolin were negativelycorrelated with urinary protein excretion, the correlation coefficient was-0.572(P<0.05) and-0.685(P <0.05).Blood samples DM group and the normal control group, IL-18was (116.42±13.28pg/ml) and (105.37±17.16pg/ml) respectively,Tristetraprolin were (284.77±20.61pg/ml) and (196.14±17.11pg/m), consistentwith the results of the urine specimen.Conclusion1、TTP involved in the inflammatory response in diabetic nephropathy2、TTP expression occurs before IL18, and may be considered as one of themarks of diabetic nephropathy kidney damage.