COUP-TFⅡ And Its Influence Factors In Renal Tissue Of Diabetic Kidney Disease

Background:As one of the major complications of diabetes mellitus,diabetic kidney disease(DKD)is the leading cause of end stage renal disease(ESRD),increasing the morbidity and mortality with the increase of diabetes mellitus incidence.It is essential to look into the mechanism behind DKD to develop efficient diagnosis and therapy.Chicken ovalbumin upstream promoter transcription factor(COUP-TF)II is an orphan nuclear receptor which has been clarified involvement in chronic kidney disease(CKD).However how it influence the DKD still needs to be further studied.This article aims at exploring the effect of C OUP-TFII in DKD and its relative risk factors.Purpose:We observed the expression characteristics of COUP-TFII in DKD and normal control,and the relationship between the expression level of COUP-TFII and clinical indicators were analysed to explore its effect and influence factors in DKD.Method:42 patients with DKD and 10 patients with renal tumor(negative margin)who underwent nephrectomy were enrolled.We compared the expression characteristics of COUP-TFII between DKD and normal control by immunohistochemistry,and observed the colocalization of COUP-TFII with a smooth muscle actin(αSMA).We collected all the clinical information of every patient,including gender,age,duration of diabetes mellitus,glycosylated hemoglobin(GHbA1c),fasting blood glucose(FBG),uric acid(UA),serum albumin(SAlb),cystatin c(Cys-C),serum creatinine(SCr),triglyceride(TG),total cholesterol(Cho),low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),urinary beta 2 microglobulin(Uβ2-MG),urinary microalbuminuria(U-MA),urinary albumin to creatinine ratio(UACR),duration and grade of high blood pressure,with or without coronary atherosclerotic heart disease,with or without diabetic retinopathy and diabetic neuropathy,percentage of tubular atrophy and renal interstitial fibrosis.We calculated the body mass index(BMI),estimated glomerular filtration rate(eGFR).Their pathological degrade and risk of CKD progression were determined according to the corresponding classification standard.We analysed the correlation between COUP-TFII IOD and clinical statistics respectively and its influence factors.Results:1.According to the immunohistochemistry and immunofluorescence,we discovered that the expression of COUP-TFII was higher in DKD than that of normal control,and the difference was significant(P<0.05).And COUP-TFII can colocalize with aSMA which is a biomarker of myofibroblast.2.The duration of diabetes mellitus,UA,SCr,Cys-C,U-MA,eGFR,percentage of renal tubular atrophy and interstitial fibrosis,IOD of COUP-TFII were significantly different between high progression risk and very high progression risk of CKD(P<0.05).3.The IOD of COUP-TFII was positively correlated with duration of diabetes mellitus,SCr,Cys-C,percentage of renal tubular atrophy,percentage of renal interstitial fibrosis and pathological degrade of DKD by Spearman correlation analysis(P<0.05).While the IOD of COUP-TFII was negatively correlated with eGFR(P<0.05).4.The IOD of COUP-TFII were significantly different between high SCr and low SCr by nonparametric test(P<0.05).Conclusion:1.The expression of COUP-TFII was higher in DKD than that of the normal control.And COUP-TFII can colocalize with aSMA,indicating that COUP-TFII may participate in the progression of renal fibrosis in DKD.2.The expression of COUP-TFII was correlated with duration of diabetes mellitus,SCr,Cys-C,the percentage of renal tubular atrophy,the percentage of renal interstitial fibrosis,pathological degrade and eGFR.And patients with higher SCr are more likely to have higher expression level of COUP-TFII,indicating that with the progression of DKD,the expression of COUP-TFII will increase correspondingly.