Distinctive gene expression profiles characterize donor biopsies from HCV-positive kidney donors.
Distinctive gene expression profiles characterize donor biopsies from HCV-positive kidney donors.
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DOI：
10.1097/tp.0b013e3181f9ca6c
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发表时间：
2010-12-15
期刊：
影响因子：
6.2
通讯作者：
Maluf DG
中科院分区：
文献类型：
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作者：
Mas VR;Archer KJ;Suh L;Scian M;Posner MP;Maluf DG
由于移植器官的短缺，从扩展标准供体（ECD）中获取肾脏是不可避免的。经常使用感染丙型肝炎病毒（HCV）的供体。为了阐明HCV移植物中分子途径的初步妥协，评估了基因表达（GE）谱。在植入前收集24例供体同种异体移植物活检（N=12 HCV（+）和N=12 HCV（-）），并使用微阵列进行分析。供者年龄种族性别、冷缺血和热缺血时间组间匹配。使用affy Bioconductor包将探针水平数据读入R编程环境中，并使用稳健的多阵列平均法获得探针组表达总结。为了鉴定表现出差异表达的探针组，进行双样品t检验。分子和生物学功能进行了分析，使用相互作用网络和功能分析。58个探针组在HCV（+）与HCV（-）供体之间差异表达（p<0.001）。与来自差异表达基因分析的两个得分最高的网络相关的分子功能是结缔组织发育和功能以及组织形态（得分34）、细胞死亡、细胞信号传导、细胞组装和组织（得分32）。在差异影响的顶级经典途径中，我们发现RIG 1样受体在抗病毒先天免疫（p值<0.001）、自然杀伤细胞信号传导（p值=0.007）、IL 8信号传导（p值=0.048）、干扰素信号传导（p值= 0.011）（INFA 21、INFGR 1、MED 14）、ILK信号传导（p值=0.001）和凋亡信号传导中的作用。在HCV（+）肾移植物中发现了独特的GE模式。先天免疫系统和炎症途径受影响最大。
Due to the shortage of organs for transplantation, procurement of kidneys from extended criteria donors (ECD) is inevitable. Frequently, donors infected with hepatitis C virus (HCV) are used. To elucidate an initial compromise of molecular pathways in HCV graft, gene expression (GE) profiles were evaluated. Twenty-four donor allograft biopsies (N=12 HCV (+) and N=12 HCV (–)) were collected at pre-implantation time and profiled using microarrays. Donors were age-race-gender, cold ischemia and warm ischemia time matched between groups. Probe level data were read into the R programming environment using the affy Bioconductor package and the robust multiarray average method was used to obtain probe set expression summaries. To identify probe sets exhibiting differential expression, a two sample t-test was performed. Molecular and biological functions were analyzed using Interaction Networks and Functional Analysis. Fifty-eight probe sets were differentially expressed between HCV (+) vs. HCV (–) donors (p<0.001). The molecular functions associated with the two top scored networks from the analysis of the differentially expressed genes were connective tissue development and function and tissue morphology (score 34), cell death, cell signaling, cellular assembly and organization (score 32). Among the differentially affected top canonical pathways we found role of RIG1-like receptors in antiviral innate immunity (p-value<0.001), natural killer cell signaling (p-value=0.007), IL8 signaling (p-value=0.048), interferon signaling (p-value=0.0 11) (INFA21, INFGR1, MED14), ILK signaling (p-value=0.001) and apoptosis signaling. A unique GE pattern was identified in HCV (+) kidney grafts. Innate immune system and inflammatory pathways were the most affected.