Time course of gene expression profiling in the liver of experimental mice infected with Echinococcus multilocularis.
Time course of gene expression profiling in the liver of experimental mice infected with Echinococcus multilocularis.
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多房棘球绦虫感染实验小鼠肝脏基因表达谱的时程分析
DOI：
10.1371/journal.pone.0014557
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发表时间：
2011-01-19
期刊：
影响因子：
3.7
通讯作者：
Wen H
中科院分区：
文献类型：
--
作者：
Lin R;Lü G;Wang J;Zhang C;Xie W;Lu X;Mantion G;Martin H;Richert L;Vuitton DA;Wen H
泡型棘球蚴病（AE）是一种严重的慢性寄生虫病，其表现类似于生长缓慢的肝癌。临床观察表明，多房棘球绦虫（E. multilocularis）这种寄生虫会影响肝脏内稳态和肝细胞代谢。然而，在实验小鼠继发性棘球蚴病的常用模型中，在感染过程中从未对此进行过分析。
在易感小鼠肝脏注射多房棘球绦虫中绦期幼虫后1、2、3和6个月，利用DNA微阵列分析评估基因表达谱。在不同时间点收集数据以监测基因表达的动态行为。在一个或多个时间点鉴定出557个差异表达基因，包括351个上调基因和228个下调基因。时间进程分析表明，在多房棘球绦虫感染初期（第1 - 2个月），大多数上调的通路与免疫过程和细胞运输有关，比如趋化因子、丝裂原活化蛋白激酶（MAPK）信号通路，而下调的通路与外源性物质代谢有关；在中期（第3个月），MAPK信号通路得以维持，并且过氧化物酶体增殖物激活受体（PPAR）信号通路出现；在后期（第6个月），大多数上调的通路与PPAR信号通路、补体和凝血级联反应有关，而下调的通路与细胞色素P450对外源性物质的代谢有关。对随机选取的19个基因进行定量逆转录聚合酶链反应分析，证实了微阵列数据的可靠性。免疫组织化学分析表明，从2个月到6个月，多房棘球绦虫感染小鼠的肝脏中增殖细胞核抗原（PCNA）增加。
多房棘球绦虫中绦期幼虫通过改变许多基因表达和代谢通路，确实对肝脏内稳态产生了深远影响。它尤其促进肝细胞增殖，正如我们在所有研究的实验时间点都不断发现PCNA增加以及关键代谢通路的基因表达增加所证明的那样。
Background Alveolar echinococcosis (AE) is a severe chronic parasitic disease which behaves like a slow-growing liver cancer. Clinical observations suggest that the parasite, Echinococcus multilocularis (E. multilocularis) influences liver homeostasis and hepatic cell metabolism. However, this has never been analyzed during the time course of infection in the common model of secondary echinococcosis in experimental mice. Methodology/Principal Findings Gene expression profiles were assessed using DNA microarray analysis, 1, 2, 3 and 6 months after injection of E. multilocularis metacestode in the liver of susceptible mice. Data were collected at different time points to monitor the dynamic behavior of gene expression. 557 differentially expressed genes were identified at one or more time points, including 351 up-regulated and 228 down-regulated genes. Time-course analysis indicated, at the initial stage of E. multilocularis infection (month 1–2), that most of up-regulated pathways were related to immune processes and cell trafficking such as chemokine-, mitogen-activated protein kinase (MAPK) signaling, and down-regulated pathways were related to xenobiotic metabolism; at the middle stage (month 3), MAPK signaling pathway was maintained and peroxisome proliferator-activated receptor (PPAR) signaling pathway emerged; at the late stage (month 6), most of up-regulated pathways were related to PPAR signaling pathway, complement and coagulation cascades, while down-regulated pathways were related to metabolism of xenobiotics by cytochrome P450. Quantitative RT-PCR analysis of a random selection of 19 genes confirmed the reliability of the microarray data. Immunohistochemistry analysis showed that proliferating cell nuclear antigen (PCNA) was increased in the liver of E. multilocularis infected mice from 2 months to 6 months. Conclusions E. multilocularis metacestode definitely exerts a deep influence on liver homeostasis, by modifying a number of gene expression and metabolic pathways. It especially promotes hepatic cell proliferation, as evidenced by the increased PCNA constantly found in all the experimental time-points we studied and by an increased gene expression of key metabolic pathways.
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影响因子：
14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R
DOI：
10.1016/0192-0561(94)90094-9
发表时间：
1994-09-01
期刊：
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY
影响因子：
--
作者：
ARMSTRONG, SG;RENTON, KW
通讯作者：
RENTON, KW
影响因子：
6.5
作者：
Chawla, M;Vishwakarma, RA
通讯作者：
Vishwakarma, RA
影响因子：
2.6
作者：
Deplazes, P;Grimm, F;Kapel, CMO
通讯作者：
Kapel, CMO
影响因子：
2.1
作者：
De-Oliveira, Ana C. A. X.;Da-Matta, Anndressa C.;Pauragartten, Francisco J. R.
通讯作者：
Pauragartten, Francisco J. R.