Park Walter, Griffin Matthew, Grande Joseph P, Cosio Fernando, Stegall Mark D
Department of Surgery, Division of Transplant Surgery, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Transplantation. 2007 Jun 15;83(11):1466-76. doi: 10.1097/01.tp.0000265501.33362.d3.
Factors contributing to kidney transplant fibrosis remain incompletely understood, particularly in the absence of acute complications.
Baseline and 1-year surveillance biopsies from 15 uncomplicated living donor kidney transplants were subjected to microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses to examine changes in gene expression patterns over time. Biopsy pairs were purposefully selected from allografts with no history of acute complications and were divided into those that were histologically normal (n=7) and those that had developed subclinical interstitial fibrosis (n=8) at 1 year.
Compared with the paired baseline specimens, expression levels of 3578 probesets were found altered in all the 1-year biopsies studied. A large proportion of the up-regulated genes in this transplant-associated profile were functionally linked with inflammation, immunity, or response to injury. These included components of inflammation-related signaling pathways (integrin, interferon, and Toll-like receptor) as well as individual mediators of inflammatory and immune responses. An additional 2884 probesets demonstrated altered expression in fibrotic grafts only at 1 year. The gene products in this fibrosis-associated profile also were predominantly linked with inflammation and immune function, suggesting exaggerated inflammatory activity within the fibrotic grafts. qRT-PCR analyses confirmed the predicted expression patterns for selected transcripts from the microarray profiles.
Transcriptional profiles of histologically normal living donor renal allografts indicate that there is ongoing injury response and inflammation at 1 year compared to the immediate posttransplant period. Subclinical development of interstitial fibrosis during the first posttransplant year is associated with additional up-regulation of inflammation-related genes.
导致肾移植纤维化的因素仍未完全明确，尤其是在没有急性并发症的情况下。
对15例无并发症的活体供肾移植受者的基线活检标本和1年监测活检标本进行微阵列和定量逆转录聚合酶链反应（qRT-PCR）分析，以检测基因表达模式随时间的变化。活检配对标本特意选自无急性并发症病史的同种异体移植肾，并分为组织学正常组（n = 7）和在1年时出现亚临床间质纤维化组（n = 8）。
与配对的基线标本相比，在所研究的所有1年活检标本中，发现3578个探针集的表达水平发生了改变。在这种与移植相关的表达谱中，很大一部分上调基因在功能上与炎症、免疫或损伤反应相关。这些包括炎症相关信号通路的成分（整合素、干扰素和Toll样受体）以及炎症和免疫反应的单个介质。另外2884个探针集仅在1年时在纤维化移植物中显示出表达改变。这种与纤维化相关的表达谱中的基因产物也主要与炎症和免疫功能相关，表明纤维化移植物中存在过度的炎症活动。qRT-PCR分析证实了微阵列谱中所选转录本的预测表达模式。
组织学正常的活体供肾移植肾的转录谱表明，与移植后即刻相比，1年时存在持续的损伤反应和炎症。移植后第一年亚临床间质纤维化的发生与炎症相关基因的进一步上调有关。
