| Background Diabetic nephropathy is one of the main chronic microvascular complications of type 2 diabetes mellitus,has increased significantly in the world in recent years.The latest research indicates that diabetic nephropathy has become the first cause of end-stage renal disease.YAP(Yes-associated protein)is critical transcriptional co-activators of the Hippo pathway involved in many pathophysiological processes,such as the regulation of organ size,cell proliferation,differentiation,apoptosis,epithelial-mesenchymal transition and cell contact inhibition.Recently,the study of YAP in diabetic nephropathy has been received much attention.YAP plays an important role in the progression of diabetic nephropathy.Therefore,to clarify the expression of yap pathway in diabetic nephropathy provides a new theoretical basis for further clarifying the pathogenesis,diagnosis and treatment.Objective By studing the expression of YAP pathway in renal tissues of patients with type 2 diabetic nephropathy and normal people,and evaluating the relationship between YAP expression in type 2 diabetic nephropathy and clinical indicators,in order to explore the expression of YAP in type 2 diabetic nephropathy and its correlation with clinical indicators,and provide ideas for delaying the progress of type 2 diabetic nephropathy.Methods This study enrolled 51 patients with type 2 diabetic nephropathy and 10 patients with renal tumor.By immunohistochemistry to measure the expressions and location of YAP,TEAD(Tea domain)and CTGF(Connective tissue growth factor)in renal tissue of the former and normal renal tissue of the latter.The patient’s information of that above type 2 diabetic nephropathy group was collected:gender,age,course of disease,systolic pressure,urinary microalbuminuria,urinary protein,urinary albumin creatinine ratio,serum albumin,fasting blood glucose,glycosylated hemoglobin,triglyceride,total cholesterol,low density lipoprotein cholesterol,high density lipoprotein cholesterol,blood urea nitrogen,serum creatinine,uric acid,glomerular filtration rate,cystatin c.According to the diabetic nephropathy staging standard,the type 2 diabetic nephropathy group was staged.According to the staining degree of YAP,TEAD,CTGF and stained cells percentage:0 points without colorimeter,1 point with lighter colorimeter and 2 points with darker colorimeter;The percentage of colored cells:0%～5%scored 0,6%～25%scored 1,26%～50%scored 2,and ≥51%scored 3.The final score was as follows:0 behaved negative,1～4 behaved weakly positive,and>4 behaved positive.Spss 22.0 software was used for statistical comparison and analysis.Results1.Normally,YAP was expressed in the cytoplasm of glomeruli and renal tubular cells in normal renal tissues,so brown granules could be found in a few nuclei.In type 2 diabetic nephropathy,the expression of YAP in glomerulus and renal tubular cells was significantly increased.There was statistical difference in YAP score between the two groups(p<0.05).2.In normal renal tissues,TEAD was mainly expressed in the nuclei of glomeruli and renal tubular cells,while in renal tissues of patients with type 2 diabetic nephropathy,the expression of YAP was increased in the nuclei of glomeruli and renal tubular cells,which was statistically different from that of normal renal tissues(p<0.05).3.In normal kidney tissues,CTGF was slightly expressed in cytoplasm and nucleus of glomeruli and renal tubular cells.While the expression of CTGF in nucleus of glomerulus and renal tubular cell nucleus was increased in type 2 diabetic nephropathy,which was statistically different from that of normal renal tissues(p<0.05).4.The expression of YAP in nucleus of glomeruli and renal tubules of patients with type 2 diabetic nephropathy was positively correlated with TEAD expression and positively correlated with CTGF expression(Spearman,p<0.05).5.According to the results of normal test,One-way analysis of variance(ANONA)or nonparametric test showed that U-MA,urinary protein,UAcr,Alb,TG,TC,Cr,UA and eGFR were significantly different in different stages of diabetic nephropathy(p<0.05).6.The expression of YAP was positively correlated with systolic blood pressure,blood urea nitrogen,serum creatinine,diabetic nephropathy stage,and negatively correlated with serum albumin,and glomerular filtration rate(Spearman,p<0.05).7.Univariate analysis showed that there were higher UAcr,Alb,Cr and DN stages in high YAP expression group than low YAP expression group(p<0.05).8.Multivariate logistic regression analysis showed that higher DN stage and Cr were was corrected with high expression of YAP(p<0.05).Conclusions1.The expression of YAP,TEAD and CTGF in patients with type 2 diabetic nephropathy is significantly increased,especially in the nucleus.The expression of YAP is correlated with TEAD and CTGF.The YAP-TEAD-CTGF pathway is active in type 2 diabetic nephropathy.2.The expression of YAP is correlated with systolic blood pressure,urea nitrogen,creatinine and serum albumin.Controlling systolic blood pressure,reducing urea nitrogen and creatinine and increasing serum albumin may reduce the risk of high expression of YAP.3.The expression of YAP is correlated with the stage of diabetic nephropathy and glomerular filtration rate,so high expression of YAP can aggravate renal damage,suggesting that inhibiting the activity of YAP may have the effect of delaying the progress of type 2 diabetic nephropathy. |
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