Expression Of Forkhead Box C2 In Rat Kidney After Unilateral Ureteral Obstruction And Its Significance

Objective:To observe the expression of transcription factor forehead box C2（FOXC2）in unilateral ureteral obstruction（UUO）rat model and study the mechanism of epithelial-mesenchymal transition（EMT）in renal tubular epithelial cells.Method:Forty-eight male Wistar rats（120-150g）were randomly divided into two groups,sham-operated group（sham,n=24 undergoing the left ureter dissection）and UUO group（UUO,n=24,undergoing the left ureteral ligation）.On the 3^rd,7^th,14^th and 21^st day after the operation,6 rats in the different groups were sacrificed for the sampling of the left kidney tissues.The histopathological changes were observed by HE and Masson staining.The expression of E-cadherin protein andα-SMA protein was detected by Western blot and immunohistochemistry.The expression of FOXC2 protein and mRNA was detected by Western blot,immunohistochemistry and real-time PCR.Results:1、Compared with the sham group,21d kidney gross of UUO group showed a significant increase in kidney volume,pale appearance,ischemic necrosis on the surface,open the kidney,there are obvious hydronephrosis,renal cortex thinning,peel pulp line not clear.2、HE results showed that the rats renal glomeruli and tubules were normal in each sham group,no inflammatory cell infiltration.With the prolongation of ureteral obstruction on rats of UUO group,tubular epithelial cells gradually appear disorder,swelling,vacuolar variants,atrophy,luminal expansion,interstitial inflammatory cell infiltration.3、Masson staining showed that as the time of ureteral obstruction on,interstitial widening,collagen fibers increased significantly,the degree of fibrosis gradually increased.4、Both immunohistochemistry and Western blot showed that the protein of E-cadherin was decreased（P<0.05）and the protein ofα-SMA was increased（P<0.05）with the obstruction time prolonged,which indicated that EMT occurred in renal tubular epithelial cells,with the obstruction time prolonged,the degree of fibrosis increased.5、Researches shows that the expression of FOXC2mRNA in each sham group has not statistical significance（P>0.05）,compared each UUO group with shame group,the difference has statistical significance（P<0.05）and an up-regulated expression of both FOXC2 mRNA and protein,reaching to the peak on the 7^th day followed by a trend of decrease up to the 21^st day.6、Immunohistochemistry and Western blotting all shows that compared with that in the sham group,an up-regulated expression of FOXC2 protein（P<0.05）,reaching to the peak on the 7^th day followed by a trend of decrease up to the 21^st day.but there was no significant change in shame group.Conclusion:With the ureteral obstruction time Prolonged,EMT was occurred on rat renal tubular epithelial cells,and FOXC2 may promote the EMT of tubular epithelial cells and be involved in the process of renal fibrosis.