Mannon R B
Transplantation Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Am J Transplant. 2006 May;6(5 Pt 1):867-75. doi: 10.1111/j.1600-6143.2006.01261.x.
The dramatic improvements in short-term graft survival and acute rejection rates could only have been dreamed of 20 years ago. Late graft loss following kidney transplantation is now the critical issue of this decade. Frequently, graft loss is associated with the development of tubular atrophy and interstitial fibrosis within the kidney (i.e. chronic allograft nephropathy; CAN). Major treatment strategies in this disorder are non-specific and the focus of intervention has been on limiting injurious events. Following graft injury is a fibrogenesis phase featuring both proliferative and infiltrative responses mediated by chemokines, cytokines and growth factors. In particular, TGFbeta has been strongly implicated in the pathogenesis of chronic injury and epithelial-mesenchymal transformation (EMT) may be part of this process. The cascade of events results in matrix accumulation, due to either increased production and/or reduced degradation of matrix. Recent investigations into the pathogenesis of tissue fibrosis have suggested a number of new strategies to ameliorate matrix synthesis. While the majority of therapies have focused on TGFbeta, this may not be an ideal maneuver in transplant settings and alternative targets identified in other fibrotic diseases will be discussed. Attacking graft fibrosis should be a new focus in organ transplantation.
短期移植肾存活和急性排斥反应率的显著提高在20年前还只是梦想。肾移植后晚期移植肾丢失是这十年的关键问题。通常，移植肾丢失与肾内肾小管萎缩和间质纤维化的发展有关（即慢性移植肾肾病；CAN）。这种疾病的主要治疗策略是非特异性的，干预重点一直是限制有害事件。移植肾损伤后是一个纤维化阶段，其特征是由趋化因子、细胞因子和生长因子介导的增殖和浸润反应。特别是，转化生长因子β（TGFβ）与慢性损伤的发病机制密切相关，上皮-间质转化（EMT）可能是这一过程的一部分。一系列事件导致基质积累，这是由于基质产生增加和/或降解减少所致。最近对组织纤维化发病机制的研究提出了一些改善基质合成的新策略。虽然大多数治疗方法都集中在TGFβ上，但在移植环境中这可能不是一个理想的策略，本文将讨论在其他纤维化疾病中确定的替代靶点。对抗移植肾纤维化应成为器官移植的新重点。
