The Expression And Significance Of Protein Related To Epithelial-Mesenchymal Transition In Renal Interstitial Fibrosis

Background:A common pathway to end stage renal failure (ESRF) caused by all kinds of kidney diseases is renal interstitial fibrosis and sclerosis, which lead to the loss of effective nephron and the progressive decline of renal function. It has been not clear at present how to happen does the mechanism of renal interstitial fibrosis, which is the hot issue all the time. Epithelial-mesenchymal transition (EMT) is a process that epithelial cells with the polarity transform to mesenchymal cells by various factors and signaling pathways. EMT is charactered by the down expression or disappear of epithelial cell phenotype protein (such as E-cadherin and β-catenin) and high expression or emerging of mesenchymal cell phenotype protein (such as a-SMA). The research about animal model of CKD in recent years reveals that renal interstitial inflammatory cells are infiltrating, and epithelial cells are forming myofibroblasts cells by phenotypic changes in the action of profibrogenic growth factor and cytokines. Then myofibroblasts are producing and secreting lots of extracellular matrix (ECM) which promotes renal interstitial fibrosis. Objective:By observing the expression of EMT-related protein E-cadherin, β-catenin and a-SMA in60patients with different kidney diseases accepting renal biopsy, we investigated the relationship between EMT and renal interstitial fibrosis, and compared the expression of EMT-related protein in different pathological types of kidney diseases. Methods:Sixty patients were collected in our study in Qilu hospital of Shandong University from Oct.2010to Oct.2011, Serum creatinine (Scr) was measuremented., We got the renal tissue by renipuncture, which were fixed, embedded in paraffin and sliced. Then we observed changes of renal pathology by HE, PAS and MASSON staining, and the damages of tubulointerstitial by half-quantitative analysis, group all cases according to the score of renal interstitial fibrosis. To observe the different expression of EMT-related protein in different kidney diseases.Results:(1) With the increase of renal interstitial fibrosis score, the expression of E-cadherin and β-catenin gradually decreased, with a gradual increase in the expression of a-SMA. There were significant difference(P<0.01) between TID2and TID0、TID1, TID3and TID0、TID1、TID2, while there was no significant difference between TID0and TID1(P>0.05).(2) There was a significant difference (P<0.05) in the degree of renal interstitial fibrosis between any two groups except MCN and MN, and the score of renal interstitial fibrosis in SGN was significantly higher than other groups. There was also a significant difference (P<0.05) between FSGS and any other groups, apart from compared to MsPGN (P>0.05). In SGN group, the expression of a-SMA was significantly increased compared with other groups, and the expression of E-cadherin and β-catenin was significantly reduced (P<0.05). There was a significant difference (P<0.05) between FSGS and any other groups about the expression of three markers, apart from compared to MsPGN (P>0.05).(3)The level of Scr was positively correlated with renal interstitial fibrosis. There was negative correlation with the points of positive expression of E-cadherin and β-catenin, and positive correlation with the a-SMA-positive expression points. There was no significant difference (P>0.05) between TID0and TID1. The other pairwise were significantly different (P<0.05).Conclusion:Epithelial-mesenchymal transition is the important mechanism of renal interstitial fibrosis. Along with the severity of renal interstitial fibrosis, the expression of epithelial phenotype protein E-cadherin and β-catenin gradually decreased, while the mesenchymal phenotype protein a-SMA gradually increased, and thus losing its epithelial polarity and cell adhesion, access to metastasis and invasion ability. EMT was only related with the degree of renal interstitial fibrosis, regardless of the glomerular pathological type. There was a certain relevance between EMT and the level of Scr, and its related proteins can be used to determine the prognosis of kidney disease and to guide further treatment.