Regulation of molecular pathways in ischemia-reperfusion injury after liver transplantation.
Regulation of molecular pathways in ischemia-reperfusion injury after liver transplantation.
复制标题
DOI：
10.1097/tp.0b013e3182a20398
复制
发表时间：
2013-11-27
期刊：
影响因子：
6.2
通讯作者：
Maluf DG
中科院分区：
文献类型：
--
作者：
Gehrau RC;Mas VR;Dumur CI;Ladie DE;Suh JL;Luebbert S;Maluf DG
缺血/再灌注（I/R）损伤是一种多因素的现象，发生在移植过程中，经常危及肝移植（LT）后早期移植物功能。目前对I/R损伤的分子机制和调控过程的理解尚不清楚。microRNA（miRNA）调控在几个生物过程中至关重要。患者和方法：本研究使用微阵列评估了在植入前（L1）和再灌注后90分钟（L2）收集的34个移植物活检组织中的基因表达和microRNA（miRNA）表达谱。首先分析了miRNA谱。数据整合分析（基因表达/microRNA表达）旨在从L1/L2差异基因表达谱中鉴定每个鉴定的miRNA的潜在靶基因。成对比较分析确定了40个miRNAs和3,168个在再灌注后与再灌注前相比显著差异表达的基因。miRNA的通路分析将这些谱与抗凋亡、抑制细胞增殖和促炎过程相关联。靶标分析鉴定了2，172个基因的miRNA相关分子谱，这些基因通过细胞周期调节、细胞死亡和存活以及促炎和抗炎过程参与细胞生长和增殖调节。miRNA非依赖性基因涉及促炎分子。我们确定了一个参与转录后调控机制的miRNA谱，在I/R损伤后LT。更好地了解这些参与I/R的分子过程可能有助于开发新的策略，以尽量减少移植物损伤。
Ischemia/reperfusion (I/R) injury is a multifactorial phenomenon that occurs during the transplant event and frequently compromise early graft function after liver transplantation (LT). Current comprehension of molecular mechanisms and regulation processes of I/R injury lacks clarity. MicroRNA (miRNA) regulation results critical in several biological processes. Patients and Methods: This study evaluated gene expression and microRNA (miRNA) expression profiles using microarrays in 34 graft biopsies collected at pre-implantation (L1) and at 90 minutes post-reperfusion (L2) from consecutives deceased donor LT recipients. MiRNA profiles were first analyzed. Data integration analysis (gene expression / microRNA expression) aimed to identify potential target genes for each identified miRNA from the L1/L2 differential gene expression profile. Pairwise comparison analyses identified 40 miRNAs and 3,168 significantly differentially expressed genes at post-reperfusion time compared with pre-reperfusion time. Pathway analysis of miRNAs associated these profiles with anti-apoptosis, inhibition of cellular proliferation, and pro-inflammatory processes. Target analysis identified a miRNA-associated molecular profile of 2,172 genes involved in cellular growth and proliferation modulation by cell cycle regulation, cell death and survival, and pro- and anti-inflammatory processes. MiRNA-independent genes involved pro-inflammatory molecules. We identified a miRNA profile involved in post-transcriptional regulatory mechanisms in I/R injury post-LT. A better understanding of these molecular processes involved in I/R may contribute to develop new strategies to minimize graft injury.