Acute Cellular Rejection Elicits Distinct MicroRNA Signatures in Airway Epithelium of Lung Transplant Patients
Acute Cellular Rejection Elicits Distinct MicroRNA Signatures in Airway Epithelium of Lung Transplant Patients
复制标题
DOI：
10.1097/txd.0000000000000551
复制
发表时间：
2015-11-01
影响因子：
2.3
通讯作者：
Chen, Peter
中科院分区：
文献类型：
--
作者：
Gharib, Sina A.;Edelman, Jeffery D.;Chen, Peter
急性细胞排斥反应（ACR）是肺移植中常见的并发症，与慢性移植物功能障碍的风险增加有关。microRNA是细胞转录的关键控制器，其表达可以在疾病状态下改变。这项初步研究的目的是评估从气道刷取的上皮细胞的microRNA谱是否可以区分患有ACR的肺移植患者和没有排斥反应的患者。我们研究了21名受试者（10名患有ACR，11名没有ACR），并评估了他们气道上皮中超过700种microRNA的表达。我们鉴定了117种差异表达的microRNA，这些microRNA将两组严格分离，并且在ACR患者中一致下调。利用实验验证的microRNA靶点，我们系统地绘制了由ACR诱导的microRNA调控的途径和过程，并注意到参与发育、增殖、迁移和修复的程序的丰富。总的来说，我们的研究表明，ACR与一个独特的上皮microRNA签名，可以提供深入了解急性排斥反应的发病机制，并可能作为一个敏感的，微创的生物标志物工具，诊断和肺移植患者的预后分层。
Acute cellular rejection (ACR) is a common complication in lung transplantation and associated with increased risk of chronic allograft dysfunction. MicroRNAs are critical controllers of cellular transcription whose expression can be altered in disease states. The purpose of this pilot study was to evaluate whether microRNA profiling of epithelial cells obtained from airway brushings can distinguish lung transplant patients with ACR from those without rejection. We studied 21 subjects (10 with ACR, 11 without ACR) and assessed the expression of over 700 microRNAs in their airway epithelium. We identified 117 differentially expressed microRNAs that robustly segregated the 2 groups and were uniformly downregulated in patients with ACR. Leveraging experimentally verified microRNA targets, we systematically mapped pathways and processes regulated by ACR-induced microRNAs and noted enrichment of programs involved in development, proliferation, migration, and repair. Collectively, our study suggests that ACR is associated with a distinct epithelial microRNA signature that can provide insight into the pathogenesis of acute rejection and potentially serve as a sensitive, minimally invasive biomarker tool for diagnostic and prognostic stratification of lung transplant patients.