Ray M, Dharmarajan S, Freudenberg J, Zhang W, Patterson G A
Washington University School of Engineering, Department of Computer Science and Engineering, St. Louis, MO, USA.
Am J Transplant. 2007 Oct;7(10):2396-405. doi: 10.1111/j.1600-6143.2007.01918.x.
Lung transplantation is the treatment of choice for end-stage pulmonary diseases. A limited donor supply has resulted in 4,000 patients on the waiting list. Currently, 10-20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15-25% fail due to primary graft dysfunction (PGD). This has spawned efforts to re-examine the current selection criteria as well as search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. From our analysis, we have obtained differentially expressed transcripts that were involved in signaling, apoptosis and stress-activated pathways. Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD.
肺移植是终末期肺部疾病的首选治疗方法。供体供应有限导致有4000名患者在等待名单上。目前,根据选择标准,提供用于移植的供体器官中有10%-20%被认为是合适的,其中15%-25%由于原发性移植功能障碍(PGD)而失败。这促使人们努力重新审视当前的选择标准,并寻找替代的供体肺选择标准。在本研究中,我们试图通过观察发生PGD的供体肺与未发生PGD的供体肺之间基因表达的变化,进一步了解PGD。通过我们的分析,我们获得了参与信号传导、细胞凋亡和应激激活途径的差异表达转录本。结果还表明,金属硫蛋白3在未发生PGD的肺中过度表达。这是首次对用于移植的实际人类肺进行表达谱分析,以鉴定PGD的分子特征。