Changes And Its Significance Of Notch Signal Pathway In Interstitial Fibrosis Of The Kidney With IgA Nephropathy

Objective:IgA nephropathy(IgAN)is one of the most common primaryglomerular disease with a variety of clinical manifestations in the world. InChina, the incidence of IgAN from25%to50%of primary glomerulonephritis,1/3of patients with progressive renal deterioration and the development ofend-stage renal failure(ESRD).But its pathogenesis is not clear. In recent years,the study found epithelial cells mesenchymal cell transformation in renalinterstitial fibrosis playing a key role in the development of IgA nephropathycan not be ignored. The important role of signaling pathway of TGF-βl inrenal interstitial fibrosis and EMT has been recognized. TGF-βl can activateboth smad signaling pathway and the smad-independent signaling pathway.Notch signaling pathway is a smad-independent signaling pathway delayedacti-vation of TGF-βl smad signaling pathway, directly in the adjacent cellsprecisely regulate signal transduction, cell proliferation, differentiation,growth and apoptosis, and participated in the occurrence and development ofmany renal disorders. The purpose of this paper is to study the change and itssignificance of Notch signal pathway in interstitial fibrosis of the kidney withIgA nephropathy.Methods:The study was approved by the Department of Nephrology of the second hospital of Hebei Medical University from2011.6to2012.8.We chosen38cases of IgA nephropathy by clinical and renal biopsy pa-thology(male22, female16;age14~60years, mean age49±8.71).The se-condary IgAN were excluded,such as purpura nephritis,systemic lupus erythematosus,Sj gren’s syndrome,HBV-GN associated glomerulonephritis Heart-failure, infection, obesity,pregnancy,live disease,Drug-inducedrenal damage.The pathological diagnosis cited by a unified IgAN Oxfordof the2009y International Association of renal pathology organizationsof developing haven good repeatability and predictability pathological type.The experimental groups:By Oxford pathological type, with or withoutglomerulosclerosis,tubular atrophy or interstitial fibrosis were divided intoT00%~25%for mild (G1,n15,male:female8:7,mean age37.93±15.873);T126%～50%for moderate(G2,n15, male:female9:6,mean age40.56±11.627);T2＞50%for severe(G3,n8,male:female5:3,mean age35.58±12.059).Thecontrol group(group C,n5cases,male:female3:2, mean age50±10.07)was form Department of Urology of the Second Hospital of Hebei Medical University.5cases of renal tumor nephrectomy but away from the si-te of the tumor of the kidney tissue,were confirmed normal renal tissueby lighmicroscope.Immunohistochemical methods stain detected kidneytissue ofNotch1,Jagged1expression and pathological image analysis to calculatethepositive goal average optical density value. Enzyme linkedimmunosorbentassay detected Notch1, Jagged1in peripheral serum of patients with IgAN.Simultaneous determined clinical index of blood bio-chemical:serumalbumin(ALB),serum cholesterol(TC),triglyceride(TG),highdensity lipoprotein(HDL-C), low density lipoprotein(LDL-C),24hour uri-nary protein(Upro),serum creatinine(Scr),uric acid(UA) and urine osmoticpressure,andevaluation of eGFR.The experimental results obtained datumwere usedSPSS13.0statistical analysis software system.The measurementdatawith the mean±standard deviation(x±s)said,for testing the normal variance,by analysis of variance(ANOVA),non-normal or variance not neat by nonparametric test,multiple comparisons between groups using Kruskal-Wallis H test,Pearson correlation test,P＞0.05level that the difference was statistically significant.Results:1Gender and age:there was no significant difference of G1, G2, G3group compared with group C (P>0.05).2Urine protein:with the disease progresses,increasing24hour urinaryprotein quantitative, there were statistically significant difference of G1, G2,G3group compared with group C (P<0.05); 3Blood lipid and plasma albumin level:TG,TC,HDL-C,LDL-C and ALBshowed no statistical difference between the four groups;4Renal function test: there were statistical significance difference inIgAN G1, G2, G3group compared with group C (P<0.05);5Notch1and Jagged1immunohistochemistry results showed:in theexperi-mental group and the control group,Notch1and Jagged1expressionmainly in the tubular proximal tubule,and the experimental group comparedwith the control group increased expression;In IgA nephropathy group,withthe disease progresses, The expression of Notch1and Jagged1in renal tubularepithelial cells were more and more,to the T2grade was the most;In thecontrol group,Notch1and Jagged1was rarely expressed.Based statisticalanalysis processing:in the renal tubules, the expression of Notch1andJagged1in the IgA nephropathy group were more than that in the controlgroup,the difference was statistically significant(P<0.05);The expression ofNotch1and Jagged1in the G3were the most, followed by the G2group,thedifference was statis-tically significant between the G3and G2groups(P<0.05).6The results of enzyme-linked immunosorbent assay for detection ofNotch1, Jagged1showed:With the development of the renal fibrosis, theexpression of Notch1and Jagged1:Notch1and Jagged1were also increased,there was significant difference between groups of Notch1(P<0.05);there wasno significant difference between G2and G3of Jagged1,there was astatistically significant differences between the other groups (P<0.05).7Correlation analysis:Notch1expression with Jagged1expression, uricacid, Scr,24urinary protein was positively correlated (r=0.869, r=0.440,r=0.633, r=0.598,P<0.01)and with urine osmolality,eGFR was negativelycorrelated (r=-0.612,r=-0.635P<0.01); no significant difference with ALB andBMI (P>0.05).In addition, the expression of Jagged1were positivelycorrelated with uric acid, Scr,24urinary protein(r=0.413r=0.836r=0.480,P<0.01),and with urine osmolality,eGFR was negatively correlated (r=-0.573,r=-0.569P <0.01), no statistical significance with ALB, BMI (P>0.05). Conclusions:the expression of Notch1and Jagged1in renal tissue andperipheral serum patients with IgA nephropathy was increased, with thedevelopment of renal tubular atrophy,renal interstitial fibrosis,suggesting thatNotch/Jagged signal transduction pathway may be activated in the IgAnephropathy,and participated in the occurrence and development of the renaltubular atrophy, interstitial fibrosis.