Epithelial-to-mesenchymal transition of human proximal tubular epithelial cells: Effects of rapamycin, mycophenolate, cyclosporin, azathioprine, and methylprednisolone
Epithelial-to-mesenchymal transition of human proximal tubular epithelial cells: Effects of rapamycin, mycophenolate, cyclosporin, azathioprine, and methylprednisolone
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DOI：
10.1097/01.tp.0000255680.71816.aa
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发表时间：
2007-03-27
期刊：
影响因子：
6.2
通讯作者：
Pilmore, Helen L.
中科院分区：
文献类型：
--
作者：
Copeland, Justin W. G. V.;Beaumont, Brent W.;Pilmore, Helen L.
肾近端小管上皮细胞（PTEC）向肌成纤维细胞的上皮-间质转化（EMT）是慢性同种异体移植肾病发病的重要步骤。肾移植中常用的免疫抑制剂对EMT的影响尚不清楚。PTEC在转化生长因子- p中培养诱导EMT。采用相差显微镜、免疫细胞化学和免疫印迹法观察免疫抑制剂对细胞形态和a-平滑肌肌动蛋白的影响。用[S-35]标记法和聚丙烯酰胺凝胶电泳法研究了对花蜜苷的影响。雷帕霉素和霉酚酸酯（MMF）阻止EMT，并使肌成纤维细胞恢复到PTEC形态。这些免疫抑制剂也减少了PTEC和肌成纤维细胞的versican产生。环孢素A、硫唑嘌呤和甲基强的松龙的效果不如雷帕霉素和MMF。此外，这些免疫抑制剂并没有降低versican。雷帕霉素和MMF对体外EMT的抑制作用比较老的免疫抑制剂更大，可能导致更少的纤维化和更好的长期同种异体移植物存活。
Epithelial-to-mesenchymal transition (EMT) of renal proximal tubular epithelial cells (PTEC) into myofibroblasts is an important step in the pathogenesis of chronic allograft nephropathy. The effects of commonly used immuno-suppressives in renal transplantation on EMT are not known. PTEC were cultured in transforming growth factor-P to induce EMT. The effects of the immunosuppressives on cell morphology and a-smooth muscle actin were studied by phase contrast microscopy, immunocytochcmistry, and western blotting. The effects on versican were studied by [S-35] labeling and polyacrylamide gel electrophoresis. Rapamycin and mycophenolate mofetil (MMF) prevented EMT and moreover returned myofibroblasts to PTEC morphology. These inummosuppressives also reduced versican production by both PTEC and myofibroblasts. Cyclosporine A, azathioprine, and methylprednisolone were less effective than rapamycin and MMF. Moreover, these immunosupprcssivcs did not decrease versican. Rapamycin and MMF have a greater inhibitory effect on EMT in vitro than older inummosuppressives and may result in less fibrosis and a better long-term allograft survival.