Aresu Luca, Rastaldi Maria Pia, Pregel Paola, Valenza Federico, Radaelli Enrico, Scanziani Eugenio, Castagnaro Massimo
Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Università degli Studi di Padova, Agripolis, Padova, Italy.
Virchows Arch. 2008 Dec;453(6):617-25. doi: 10.1007/s00428-008-0684-8. Epub 2008 Oct 24.
Mechanism of renal fibrosis leading to end stage kidney remains still a challenge of interest in humans. The pathogenesis of chronic kidney disease is characterized by progressive loss of kidney function and fibrosis. The mechanism of epithelial-mesenchymal transition (EMT) has been predominantly studied in in vitro studies, and we previously demonstrated the EMT of tubular epithelial cells in dogs. In this study, we examined and quantified the modifications of cadherin-catenin complex by immunohistochemistry of E-cadherin and beta-catenin and the mesenchymal marker vimentin in 25 dogs with three different spontaneous inflammatory renal diseases. Results showed a significant down-expression of levels of E-cadherin and beta-catenin directly correlated with the tubular-interstitial damage (TID). In TID grades 2 and 3, E-cadherin expression was significantly reduced (p < 0.001). beta-catenin expression was overall similar to E-cadherin. The mesenchymal-associated protein, vimentin, was de novo identified in tubules within areas of inflammation. In this work, we identified the loss of cadherin or catenin expression as a progressive mechanism in tubulo-interstitial fibrosis, which allows dissociation of structural integrity of renal epithelia and loss of epithelial polarity. The dog might result more significant as model for new therapies.
导致终末期肾病的肾纤维化机制仍是人类关注的一个挑战性问题。慢性肾脏病的发病机制以肾功能进行性丧失和纤维化为特征。上皮-间质转化（EMT）机制主要在体外研究中得到探讨，我们之前已在犬类中证实了肾小管上皮细胞的EMT。在本研究中，我们通过对E-钙黏蛋白和β-连环蛋白进行免疫组化以及检测间充质标志物波形蛋白，对25只患有三种不同自发性炎性肾病的犬的钙黏蛋白-连环蛋白复合物修饰情况进行了检测和定量分析。结果显示，E-钙黏蛋白和β-连环蛋白水平显著下调，且与肾小管间质损伤（TID）直接相关。在TID 2级和3级时，E-钙黏蛋白表达显著降低（p < 0.001）。β-连环蛋白的表达总体上与E-钙黏蛋白相似。在炎症区域的肾小管中首次发现了间充质相关蛋白波形蛋白。在本研究中，我们确定钙黏蛋白或连环蛋白表达缺失是肾小管间质纤维化的一种渐进性机制，它会导致肾上皮结构完整性的解离和上皮极性的丧失。犬作为新疗法的模型可能更具意义。
