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  • 學位論文

p120-catenin在腎小管上皮細胞質之表現與腎間質纖維化之關係

Intensity of p120-catenin expression in normal renal tubule cytoplasm is associated with renal interstitial fibrosis

指導教授 : 張浤榮

摘要


研究背景及目的:Epithelial-mesenchymal transition (EMT)已被認為是腎間質纖維化的機轉之一。E-cadherin和β-catenin已被視為EMT的指標,和腎纖維化之關係也已被發表。但是仍有關於EMT是否不完全的爭議存在。P120-catenin (p120)具有與E-cadherin跟β-catenin的密切接觸,並對於細胞移行有影響力,因此可能在EMT佔有一席之地。因此,這一篇研究的目的要探討p120在腎小管上皮之表現與腎間質纖維化之關係。同時探討p120與E-cadherin和β-catenin之間的關係。 研究方法及資料:本篇為橫斷面之研究。有73位因為各種原因接受腎臟切除的患者納入研究當中。在排除25位個案後,有48位患者納入研究當中。接著以免疫組織染色法研究這些腎臟當中E-cadherin, β-catenin和p120的表現。再分析指標之間的相關性以及跟腎臟間質纖維化之關係。 研究結果:有較高纖維化程度之族群,其estimated glomerular filtration rate (eGFR) 較低,並有比較高的比例為urothelial cell carcinoma (UCC)以及各種發炎之診斷。指標之間的相關性分析發現,p120與E-cadherin在所有的腎小管皆有相關性,而E-cadherin和β-catenin則在萎縮腎小管的表現有相關性。單變項分析發現eGFR越低,p120在腎小管的表現越高,以及診斷為UCC或是發炎等診斷,皆與較高之纖維化程度有關係。多變項分析發現,p120在腎小管的表現,以及患者是UCC或是發炎等診斷,皆是預測腎間質纖維化之獨立因子。 研究結論:這篇研究顯示p120在正常腎臟小管細胞質之表現與腎間質纖維化之嚴重度有相關性。同時研究也顯示p120與E-cadhein這一個EMT指標在腎小管細胞質中的不正常表現也具有相關性存在。

並列摘要


Introduction:Epithelial-mesenchymal transition (EMT) has been proposed as one of the mechanism of renal interstitial fibrosis. E-cadherin and β-catenin have widely accepted as markers of EMT and the correlation with renal fibrosis has been published. But there were still debate about incomplete EMT. P120-catenin (p120) is a potentially EMT markers because it has close intact with E-cadherin and β-catenin and influence on cell migration. Therefore, the objective of this study is to investigate the association between p120 expression in renal tubular epithelium with the degrees of renal interstitial fibrosis as well as the correlation between p120 expression and other EMT markers expression including E-cadherin and β-catenin. Methods and Materials:Seventy-three patients following nephrectomy were retrospectively enrolled initially. After exclusion twenty-five patients due to various reasons forty-eight patients entered this study. Immunohistochemical analysis of the renal expression of E-cadherin, β-catenin and p120 in the nephrectomised kidneys was performed and associations between renal expression of these markers and renal interstitial fibrosis were evaluated. Results:The group with higher interstitial fibrosis scores has lower estimated GFR (eGFR) and more patients with diagnosis of urothelial cell carcinoma (UCC) and inflammation. Significant association between p120 and E-cadherin was found in all renal tubules and association between E-cadherin and β-catenin was found in atrophic renal tubules. Univariate analysis showed low eGFR, high p120 expression in normal renal tubules, and diagnosis with UCC and inflammation and are significant correlated with interstitial fibrosis. Multivariate analysis showed p120 expression in normal renal tubules, diagnosis with UCC or inflammation are independent factors predicting renal interstitial fibrosis. Conclusion:This study demonstrated that the intensity of p120 expression in normal renal tubule cytoplasm was associated with the severity of renal interstitial fibrosis. This study also demonstrated that the aberrant distribution of p120 in cytoplasm of renal tubules significantly correlated with another EMT marker, E-cadherin.

參考文獻


Ou, J. H., Pan, C. C., Lin, J. S., Tzai, T. S., Yang, W. H., Chang, C. C., Cheng, H. L., Lin, Y. M., & Tong, Y. C. (2000). Transitional cell carcinoma in dialysis patients. Eur Urol, 37(1), 90-94.
Bariety, J., Hill, G. S., Mandet, C., Irinopoulou, T., Jacquot, C., Meyrier, A., & Bruneval, P. (2003). Glomerular epithelial-mesenchymal transdifferentiation in pauci-immune crescentic glomerulonephritis. Nephrol Dial Transplant, 18(9), 1777-1784.
Bohle, A., Christ, H., Grund, K. E., & Mackensen, S. (1979). The role of the interstitium of the renal cortex in renal disease. Contrib Nephrol, 16, 109-114.
Carew, R. M., Wang, B., & Kantharidis, P. (2012). The role of EMT in renal fibrosis. Cell Tissue Res, 347(1), 103-116. doi: 10.1007/s00441-011-1227-1
Chang, C. H., Yang, C. M., & Yang, A. H. (2007). Renal diagnosis of chronic hemodialysis patients with urinary tract transitional cell carcinoma in Taiwan. Cancer, 109(8), 1487-1492. doi: 10.1002/cncr.22557

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