Department of Surgery, Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA, USA.
Am J Transplant. 2012 May;12(5):1113-23. doi: 10.1111/j.1600-6143.2011.03958.x. Epub 2012 Feb 2.
MicrorRNA are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes. In addition to being involved in many biologic processes, microRNAs are important regulators in innate and adaptive immune responses. Distinct sets of expressed microRNAs are found in different cell types and tissues and aberrant expression of microRNAs is associated with many disease states. MicroRNA expression was examined in a model of heterotopic heart transplantation by microarray analyses and a unique profile was detected in rejecting allogeneic transplants (BALB/c → C57BL/6) as compared to syngeneic transplants (C57BL/6 → C57BL/6). The microRNA miR-182 was significantly increased in rejecting cardiac allografts and in mononuclear cells that infiltrate the grafts. Forkhead box (FOX) proteins are a family of important transcription factors and FOXO1 is a target of miR-182. As miR-182 increases after transplant, there is a concomitant posttranscriptional decrease in FOXO1 expression in heart allografts that is localized to both the cardiomyocytes and CD3(+) T cells. The microRNA miR-182 is significantly increased in both peripheral blood mononuclear cells and plasma during graft rejection suggesting potential as a biomarker of graft status. Our results identify microRNAs that may regulate alloimmune responses and graft outcomes.
微小 RNA 是一种小的非编码 RNA 分子，可调节靶基因的转录后表达。除了参与许多生物学过程外，微小 RNA 还是先天和适应性免疫反应的重要调节剂。不同的细胞类型和组织中存在不同的表达微小 RNA，微小 RNA 的异常表达与许多疾病状态有关。通过微阵列分析检查了异位心脏移植模型中的微小 RNA 表达，与同基因移植（C57BL/6→C57BL/6）相比，排斥同种异体移植（BALB/c→C57BL/6）中检测到独特的微小 RNA 谱。微小 RNA miR-182 在排斥的同种异体心脏移植物和浸润移植物的单核细胞中显著增加。叉头框（FOX）蛋白是一类重要的转录因子，FOXO1 是 miR-182 的靶标。由于移植后 miR-182 增加，心脏移植物中 FOXO1 的转录后表达同时下降，定位于心肌细胞和 CD3(+)T 细胞。在排斥过程中，外周血单个核细胞和血浆中的微小 RNA miR-182 均显著增加，提示其可能作为移植物状态的生物标志物。我们的研究结果确定了可能调节同种免疫反应和移植物结局的微小 RNA。
