Expression And Significance Of U-PA On Rats With Epithelial-mesechymal Transdifferentiation

Objective To establish rat models of unilateral ureteral obstruction(UUO),and observe the expression of urokinase plasminogen activator(u-PA) in renaltissue at different stages so as to explore the correlation between the expressionof u-PA and epithelial-mesenchymal transdifferentiation(EMT)and thus toprimarily explore the significance of u-PA on EMTMethods Sixty-four normal-grade male SD rats were randomly divided intosham operation group and model group with32animals in each group. Therenal tissue was harvested for pathological analysis at3,7,14and28days afterUUO. The renal tubule damage and the disruption of renal tubularbasement(TBM) of each rat were observed on days3,7,14and28after UUO,and the immunohistochemical technique was used to dynamically observe theexpression of u-PA,E-cadherin andα-smooth muscle actin(α-SMA) in2groups. Relative observative targets were compared at different stages betweengroups and within groups. Then correlation between u-PA andα-SMA, andbetween u-PA and E-cadherin within UUO group was analyzed. Theexperimental data was analyzed by SPSS16.0statistical software.Results The renal tubule damage，renal interstitium fibrosis circumstanceand the disruption of renal tubular basement membrane(TBM) weresignificantly increased as days prolonging in UUO group(P﹤0.05). Thepositive expression of α-SMA and FN in renal tubulointerstitium weregradually increased, but which of E-cadherin gradually decreased as days prolonging in UUO group. In UUO rats, the positive expression of u-PA in renaltubulointerstitium was found at day3after operation and the expression peakedin tubulointerstitium at day7, then decreased gradually. The expression score ofu-PA in renal tubulointerstitium was negatively associated with the positive areascore of E-cadherin in the initial stage of obstruction(r=-0.993，P﹤0.05), butwhich was positively associated in the post stage(r=0.955，P﹤0.05). Theexpression score of u-PA in renal tubulointerstitium was positively associatedwith the disruption of renal tubular basement membrane (r=0.556,P﹤0.001).Conclusions①The rat models of unilateral ureteral obstruction are theideal models which are studied for epithelial-mesenchymal transdifferentiation②The expression levels of u-PA relate closely to the disruption of TBM andaccumulation of the ECM, which may play an important role in tubularepithelial-myofibroblast transdifferentiation.③In the initial stage of UUO, renaltissue maybe compensatory excrete and synthesize u-PA by themselves, whichis profit to delay the advancement of renal interstitial fibrosis more or less; withthe development of fibrosis, renal tubular epithelial cell degeneration andnecrosis were found, and the secretion of u-PA is decreased gradually.