Significance Of Epithelial To Mysenchymal Transition In Children With Steroid-resistant And Steroid-sensitive Nephrotic Syndrome

Objective:To study the expressions of p-glycoprotein(P-gp), cytokeratin(CK)and vimentin in kidney tissue of children with steroid-resistant nephrotic syndrome(SRNS)and steroid-sensitive nephrotic syndrome(SSNS),and to evaluate the role of them in glucocorticoid(GC)action and in kidney tissue pathological progression in idiopathic nephrotic syndrome(INS).Methods:Kidney tissue samples were obtained from 20 SRNS patients and 20 SSNS patients,1 nephrectomized healthy adult due to traffic accident,respectively.Those renal tissue samples were embedded in paraffin and assessed by routine pathological method.The degree of renal histopathological lesions was counted by the pahological scoring method.The different expressions of P-gp,CK and vimentin in kidney tissue in every group were measured by immunohistochemistry and double staining technique.The correlation between the expression of P-gp,CK and vimentin and the counting scores of renal histopathological lesions was analyzed.Results:①Renal pathological types-in these 40 INS cases showed mesangial proliferative glomerulonephritis(MsPGN)24 cases,minimal change disease(MCD)6 cases,focal segmental glomerulosclerosis (FSGS)5 cases,membranoproliferative glomerulonephritis(MPGN)2 cases,membranous nephropathy(MN)2 cases,scleroglomerulonephritis (SGN)1 case,respectively.②There was no significant difference in the total pahological counting scores and the glomerular pahological counting scores between SRNS and SSNS group(P＞0.05),but the tubulointerstitial pahological counting scores in SRNS group was higher than that in SSNS group(P＜0.05).③Positive expressions of P-gp in tubular epithelial cells(TEC)was higher in SRNS group than that in SSNS group and normal renal tissue(P＜0.05).④TEC in normal kidney tissue only expressed CK,but not vimentin.The expression of CK was lower,and the expression of vimentin was higher in SRNS group than that of in SSNS group and control tissue(P＜0.05).⑤The expression of P-gp was higher,and the expression of CK was lower in FSGS than that of in MsPGN and MCD(P＜0.05).⑥The expressions of P-gp,CK and vimentin varied with the degree of tubulointerstitial lesions(graded as normal,mild,moderate and severe lesions).Results showed a general tendency of increasing expressions of P-gp and vimentin,and decreasing expression of CK concomitanted of the increasing grade of tubulointerstitial lesions(P＜0.05).⑦The counting scores of the total renal histopathological lesions,the glomerular lesions,and the tubulointerstitial lesions all positively correlated with the level of P-gp and vimentin expressions,but negatively correlated with CK expression in renal tissue(P＜0.05 or P＜0.01).Furthmore,the degree of the correlation was higher in SRNS group than in SSNS group.The level of P-gp expression positively correlated with vimentin but negatively correlated with CK expression(P＜0.01).Conclusions:①The phenomenon of epithelial to mesenchymal transition(EMT)and up-regulation of P-gp expression existed differently in renal tissue from INS cases,and the degree of those in SRNS group was higher than that in SSNS group.②EMT and up-regulation of P-gp expression in renal tubular epithelial cells might play an important role in renal pathological progression and the different response to GC in INS.