The Role Of PAX2 In Unilaterral Ureteral Obstruction Rats With Renal Tubulointerstitial Fibrosis

Objective:To detect the expression of PAX2 andα-smooth muscle actin (α-SMA) in renal tissue of rats with unilateral ureteral obstruction (UUO), and investigate the role of PAX2 in renal tubulointerstitial fibrosis .Method: Forty-eight Wistar male rats (6-week-old)were randomly assigned into 2 groups , the control group and model group .The mode group′s left ureter was dissociated to be obstructed. The control group was dissociated left ureter only, and not to be obstructed. Six rats of both two groups were killed on 7, 14, 21 , 28 days after surgery respectively. Histological changes of renal tubular interstitium were observed by HE and Masson staining , and the renal interstial fibrosis index was calculated. The expression of PAX2 mRNA of renal tissue was assessed by real-time quantitative reverse transcription polymerase chain reaction, and the expression of protein of FN,Col-Ⅳ,α-SMA and PAX2 was detected by imunohistochemistry method .Result: (1) There was no predominant histological change in the control group , the fibrosis index of rats in model group was significantly increased as compared with control group at different time points(p<0.01), it was increased gradually accompanying with the increasing of degree of obstruction. (2)The expression of protein of FN and Col-Ⅳin model group was increased remarkbly compared with control group at different time points (p<0.01), accompanying with the increasing of degree of obstruction, it was increased gradually and peaked at 28th day. (3)The protein ofα-SMA was expressed in vascular smooth muscle of rats in control group, but a little was expressed in renal tubular interstitium . The protein ofα-SMA was maily expressed in renal tubular basement membrane and renal tubular interstitium in modle group.The expression of protein ofα-SMA in modle group was increased significantly compared with control group at different time points (p<0.01), and it was increased gradually accompanying with the increasing of degree of obstruction and peaked at 28th day. (4)There was a little mRNA of PAX2 expressed in renal tissue in control group, and there was no protein of PAX2 in renal tubular epithelial cell ,but there was microamount expression in glomerular capsule cell. The expression of mRNA and protein of PAX2 of renal tissue in model group was increased significantly compared with control group at different time points (p<0.01), and it was increased gradually accompanying with the increasing of degree of obstruction and peaked at 28th day. (5) There were positive correlation among the expression of protein ofα-SMA,FN,Col-Ⅳand PAX2 respectively, (r=0.880, 0.67, 0.75, all P<0.05), and the expression of protein of PAX2 andα-SMA were significantly positively correlated with the renal interstitial fibrosis index (r= 0.886, 0.918, both P<0.05),Conclusion:PAX2 may play a role of tubular epithelial- myofibroblast transdifferentiation in unilateral ureteral obstruction rats , as a result the number of the myofibroblast cell increased in renal interstitium ,which resulted in a large accumulation of extracellular matrix, then it may contribute to renal tubulointerstitial fibrosis .