Pribylova-Hribova P, Kotsch K, Lodererova A, Viklicky O, Vitko S, Volk H-D, Lacha J
Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Kidney Int. 2006 May;69(10):1872-9. doi: 10.1038/sj.ki.5000328.
Acute rejection (AR) is a dominant risk factor for developing chronic allograft nephropathy (CAN) after kidney transplantation. CAN is characterized by progressive interstitial fibrosis. It has been associated with increased transforming growth factor (TGF)-beta1 expression, however, kinetic studies are absent. We investigated whether intragraft TGF-beta1 expression in various causes of early graft dysfunction may influence late renal allograft dysfunction. A total of 174 human renal biopsies were quantified for TGF-beta1 mRNA expression using real-time reverse transcriptase-polymerase chain reaction. Expression levels were correlated with the Banff histopathological grades, TGF-beta1 immunohistology, and clinical follow-up. TGF-beta1 was most markedly upregulated in AR, CAN, and acute tubular necrosis - delayed graft function compared to non-rejecting controls (P < 0.001). TGF-beta1 expression was heightened in borderline changes (P < 0.01), recurrence of glomerulonephritis, and cyclosporine toxicity (P < 0.05). There was no correlation between intragraft TGF-beta1 expression during AR and short-term outcome of a rejection episode. TGF-beta1 gene overexpression during CAN has been shown to be associated with the increased risk for renal allograft dysfunction 18 months after biopsy (odds ratios 9.9 vs 3.2, respectively). Intragraft TGF-beta1 mRNA expression is significantly upregulated in both AR and CAN. Thus, our results support the hypothesis that TGF-beta1 might play a key role in chronic allograft dysfunction.
急性排斥反应（AR）是肾移植后发生慢性移植肾肾病（CAN）的主要危险因素。CAN的特征是进行性间质纤维化。它与转化生长因子（TGF）-β1表达增加有关，然而，缺乏动力学研究。我们研究了早期移植肾功能障碍各种病因中移植肾内TGF-β1表达是否会影响晚期移植肾功能障碍。使用实时逆转录聚合酶链反应对总共174例人类肾活检组织进行TGF-β1 mRNA表达定量。表达水平与班夫组织病理学分级、TGF-β1免疫组织学及临床随访相关。与非排斥对照组相比，TGF-β1在AR、CAN和急性肾小管坏死-移植肾功能延迟中上调最为明显（P<0.001）。在临界改变（P<0.01）、肾小球肾炎复发和环孢素毒性中TGF-β1表达升高（P<0.05）。AR期间移植肾内TGF-β1表达与排斥反应的短期结果之间无相关性。已表明CAN期间TGF-β1基因过表达与活检后18个月移植肾功能障碍风险增加相关（优势比分别为9.9对3.2）。AR和CAN中移植肾内TGF-β1 mRNA表达均显著上调。因此，我们的结果支持TGF-β1可能在慢性移植肾功能障碍中起关键作用这一假说。
