MicroRNA-gene expression network in murine liver during Schistosoma japonicum infection.
MicroRNA-gene expression network in murine liver during Schistosoma japonicum infection.
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日本血吸虫感染期间小鼠肝脏中的 MicroRNA 基因表达网络
DOI：
10.1371/journal.pone.0067037
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Cai P;Piao X;Liu S;Hou N;Wang H;Chen Q
日本血吸虫病在中国和东南亚国家是一个严重的公共卫生问题。慢性东方血吸虫病最典型和最严重的后果是宿主肝脏的进行性肉芽肿和纤维化，这一直是一个重大的医学挑战。然而，肝脏发病机制的分子机制仍然不清楚。方法和主要发现使用微阵列，我们定量的时间基因表达谱在日本血吸虫感染的BALB/c小鼠在感染后15，30和45天（dpi）与未感染的小鼠作为对照组的肝脏。与肝损伤相关的基因表达改变在感染的初始阶段（dpi 15）观察到，这与产卵开始变得更加宏伟。上调基因主要与炎症浸润相关，而下调基因主要导致肝功能障碍。同时，通过Solexa测序对来自相同样品的microRNA谱进行解码。在S.日本血吸虫感染在感染中期（dpi 30）显著失调的miRNA，例如mmu-miR-146 B和mmu-miR-155，可能与肝脏炎症反应的调节有关，而在感染晚期（dpi 45）表现出峰值表达的miRNA，例如mmu-miR-223、mmu-miR-146 a/B、mmu-miR-155、mmu-miR-34 c、mmu-miR-199、mmu-和mmu-miR-134，可能代表染色体性肝病发展的分子特征。进一步构建了感染过程中miRNA-基因共表达的动态网络。结论和意义本研究提供了一个整体的观点，在S.日本血吸虫感染，并强调miRNA可能在肝脏病理发展过程中平衡免疫反应中发挥多种调节作用。这些结果为进一步研究虫卵致肝损害的发病机制和分子生物学事件提供了可靠的信息。
Background Schistosomiasis japonica remains a significant public health problem in China and Southeast Asian countries. The most typical and serious outcome of the chronic oriental schistosomiasis is the progressive granuloma and fibrosis in the host liver, which has been a major medical challenge. However, the molecular mechanism underling the hepatic pathogenesis is still not clear. Methodology and Principal Findings Using microarrays, we quantified the temporal gene expression profiles in the liver of Schistosoma japonicum-infected BALB/c mice at 15, 30, and 45 day post infection (dpi) with that from uninfected mice as controls. Gene expression alternation associated with liver damage was observed in the initial phase of infection (dpi 15), which became more magnificent with the onset of egg-laying. Up-regulated genes were dominantly associated with inflammatory infiltration, whereas down-regulated genes primarily led to the hepatic functional disorders. Simultaneously, microRNA profiles from the same samples were decoded by Solexa sequencing. More than 130 miRNAs were differentially expressed in murine liver during S. japonicum infection. MiRNAs significantly dysregulated in the mid-phase of infection (dpi 30), such as mmu-miR-146b and mmu-miR-155, may relate to the regulation of hepatic inflammatory responses, whereas miRNAs exhibiting a peak expression in the late phase of infection (dpi 45), such as mmu-miR-223, mmu-miR-146a/b, mmu-miR-155, mmu-miR-34c, mmu-miR-199, and mmu-miR-134, may represent a molecular signature of the development of schistosomal hepatopathy. Further, a dynamic miRNA-gene co-expression network in the progression of infection was constructed. Conclusions and Significance This study presents a global view of dynamic expression of both mRNA and miRNA transcripts in murine liver during S. japonicum infection, and highlights that miRNAs may play a variety of regulatory roles in balancing the immune responses during the development of hepatic pathology. The data provide robust information for further researches on the pathogenesis and molecular events of hepatopathy induced by schistosome eggs.
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影响因子：
3.7
作者：
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通讯作者：
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Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.
影响因子：
14.9
作者：
Griffiths-Jones S;Grocock RJ;van Dongen S;Bateman A;Enright AJ
通讯作者：
Enright AJ