The Expression And Significance Of DJ-2 And PTEN In Chronic Kidney Disease

ObjectiveThere was 7% increase in the incidence of chronic kidney disease(CKD) annually,which developed into the end stage renal disease(ESRD) ultimately. Many studies have focused on the glomerular sclerosis, fibrosis and other diseases, and what should not be overlooked is that the tubulointerstitial lesions in progressive renal damage also plays a very important role. Therefore, Not only to treat the glomerular lesions is important,but also to delay or even prevent the development of tubulointerstitial lesion of chronic kidney disease has become anther topic.This experiment was intended to study the expression and significance of fibrosis factor DJ-1 (Parkinson's disease protein 7) and anti-fibrosis factor PTEN (chromosome 10 deletion on the phosphatase and tensin homologue gene) in primary renal chronic kidney disease.The relationship between PTEN, DJ-1 and clinical data, laboratory parameters, pathological changes was analyzed to explore the role of PTEN and DJ-1 in tubulointerstitial lesions, and to provide evidence to the pathogenesis and treatment of CKD.MethodsWe analyed 45 patients that have been made a definite diagnosis to Chronic Kidney Disease by renal biopsy and clinical data from December 2010 to April 2011 in urology department of Jinan Military General Hospital.There were 25 male and 20 females。Clinical diagnoses included 30 cases of chronic nephritis, 12 cases of nephrotic syndrome, 3 cases of latent glomerulonephritis.To exclude secondary chronic kidney disease,including diabetic nephropathy, purpura nephritis, hepatitis B associated glomerulonephritis, lupus nephritis, renal amyloidosis, drug-induced kidney damage and so on.Average age, body mass index, mean disease duration of patients should be collected.Observed and recorded the clinical parameters before renal biopsy in chronic kidney disease patients,such as systolic blood pressure, diastolic blood pressure, hemoglobin, 24-hour urine protein,serum albumin, serum globulin,cholesterol,triglycerides,creatinine,blood urea nitrogen,serum uric acid, urine specific gravity, urine osmolality, et al, and estimate glomerular filtration rate(GFR) by the simplified MDRD formula. Renal biopsy were divided into three parts, frozen section were treated with conventional IgA,IgG,IgM,C3,C1q,FRA,HbsAg,HbcAg immunofluorescence staining. Assayed DJ-1 (FITC labeled) and PTEN (Cy3 labeled) in renal tissue by a three-step immunofluorescence.Use the Qingdao meidixin software to semi-quantitative expression of the average immunofluorescence intensity.Second section were treated with conbentional HE,PAS,MASSON,PASM staining. And observed pathological changes under light microscope. Quantified the glomerular ,tubulointerstitial ,vascular damages by Reference Katafuchi scoring standard . Another part of tissues was treated with electron microscope.Analyzed statistical data by SPSS 13.0 statistical software,and test results expressed as ?x±s,P<0.05 as statistically significant differerce.Result1,Average age of patients (43.37±15.72) years, mean disease duration (19.65±33.83) months,average systolic blood pressure (133.17±21.75) mmHg, average diastolic blood pressure (85.17±11.33) mmHg.2,The pathology type of the 45 patients included: 1) mesangial proliferative glomerulonephritis in 20 cases: mild in 6 cases, moderate in 11 cases and severe in 3 cases; 2) membranous nephropathy in 6 cases:Ⅰtype in 1 case,Ⅱtype in 3 cases,Ⅲtype in 2 cases; 3) IgA nephropathy in 12cases:Ⅱgrade in 1 case,Ⅲgrade in 3 cases,Ⅳgrade in 5 cases,Ⅴgrade in 3 cases; 4)focal segmental glomerular sclerosis in 3cases; 5) proliferative kidney membrane small glomerulonephritis in 4 cases. According to tubulointerstitial integral divided into 4 groups:Ⅰgroup (9 cases);Ⅱgroup (15 cases);Ⅲgroup (11 cases) andⅣgroup(10cases).3,DJ-1 expressed in renal tubular epithelial cells .With the extent of tubulointerstitial lesions increased,the expression of DJ-1 increased gradually.The difference between the groups had a statistical significant(P<0.05).There was a opposite correlation between DJ-1 and glomerular filtration rate, osmolality(P < 0.05) ; the relationship of DJ-1 and tubulointerstitial damages scoring, serum creatinine, were positive(P<0.05). 4,PTEN expressed in renal tubular epithelial cells abundantly in patients without tubular lesions.With the extent of tubulointerstitial lesions increased,the expression of PTEN decreased gradually.The difference between the groups had a statistical significant (P <0.05).There was a positive correlation between PTEN and glomerular filtration rate, osmolality(P<0.05); the relationship of PTEN and tubulointerstitial damages scoring, serum creatinine was markedly opposite(P<0.05).5,The Expression of DJ-1 and PTEN in renal tissues was opposite. Statistical analysis showed a negative correlation(r=-0.823,P<0.01).Conclusion1,The expression of DJ-1 in different groups of primary Chronic Kidney Disease was different,and DJ-1 increased as tubulointerstitial fibrosis increased. The difference between the groups had a statistical significant.DJ-1 had a negatively correlated with glomerular filtration rate,urine osmolality , had a positively correlated with renal calculus,serum creatinine.There was a positive correlation between DJ-1 and renal fibrosis.2,The expression of PTEN in different groups of primary Chronic Kidney Disease was different,and PTEN decreased as tubulointerstitial damage scoring increased. The difference between the groups had a statistical significant.PTEN had a positively correlated with glomerular filtration rate,urine osmolality , had a negatively correlated with renal calculus,serum creatinine.It showed that PTEN decreased as the tubulointerstitial fibrosis increased,there was a negative correlation between them.3.,The relationship of DJ-1 and PTEN was opposite which reminded us that DJ-1 might regulate the expression of PTEN negatively in the process of renal tubulointerstitial fibrosis.