Özdemir B H, Özdemir A A, Colak T, Sezer S, Haberal M
Department of Pathology, Baskent University, Ankara, Turkey.
Transplant Proc. 2011 Mar;43(2):527-9. doi: 10.1016/j.transproceed.2011.01.017.
It has been reported that myofibroblasts are the major cells in the development of interstitial fibrosis (IF) and, therefore, chronic dysfunction in renal allografts. Our aim was two fold: first, to understand the key markers controlling tubular and glomerular epithelial-to-mesenchymal transition (EMT); second, to show the role of tubular EMT on the development of interstitial fibrosis (IF) and the role of glomerular EMT on the development of proteinuria and, therefore, graft survival. For this purpose we evaluated the vinculin- and paxillin-containing adhesion complexes and α-smooth muscle actin (α-SMA) expression on tubular cells and glomerular podocytes in first year renal allograft biopsy specimens of 74 patients. We established the proteinuric state at the time of the biopsy of all patients. Follow-up biopsy specimens of all patients were evaluated for the development of diffuse IF (≥50% of the biopsy specimen). Among 74 patients, 21 showed grade 1 and 9 showed grade 2 tubular EMT. Only 25/74 cases showed glomerular EMT. The incidence of the development of diffuse IF at 18 and 24 months after the initial biopsy and the graft loss at 5 years were higher among subjects with tubules and glomerular podocytes showing EMT (P<.001 for all). The development of IF and graft loss was significantly earlier in cases with grade 2 compared with grade 1 or no tubular EMT (P<.001 for all). The proteinuric state at the time of the biopsy showed a significant positive correlation with the glomerular EMT (P<.001). In conclusion, our results showed that renal tubular cells and glomerular podocytes can undergo epithelial-to-mesenchymal differentiation. The transformed cells with reorganized cytoskeletal features have an important role in renal allograft survival by inducing the development of diffuse IF and proteinuria.
据报道，肌成纤维细胞是间质纤维化（IF）发展的主要细胞，因此也是肾移植慢性功能障碍的主要细胞。我们的目标有两个：第一，了解控制肾小管和肾小球上皮-间质转化（EMT）的关键标志物；第二，阐明肾小管EMT在间质纤维化（IF）发展中的作用以及肾小球EMT在蛋白尿发展和移植肾存活中的作用。为此，我们评估了74例患者第一年肾移植活检标本中肾小管细胞和肾小球足细胞上含纽蛋白和桩蛋白的黏附复合物以及α-平滑肌肌动蛋白（α-SMA）的表达。我们确定了所有患者活检时的蛋白尿状态。对所有患者的随访活检标本进行弥漫性IF（≥活检标本的50%）发展情况的评估。在74例患者中，21例显示1级肾小管EMT，9例显示2级肾小管EMT。仅25/74例显示肾小球EMT。在肾小管和肾小球足细胞显示EMT的受试者中，初始活检后18个月和24个月弥漫性IF发展的发生率以及5年时移植肾丢失率更高（所有P<0.001）。与1级或无肾小管EMT的病例相比，2级病例中IF的发展和移植肾丢失明显更早（所有P<0.001）。活检时的蛋白尿状态与肾小球EMT呈显著正相关（P<0.00）。总之，我们的结果表明肾小管细胞和肾小球足细胞可发生上皮-间质分化。具有重组细胞骨架特征的转化细胞通过诱导弥漫性IF和蛋白尿的发展在肾移植存活中起重要作用。
