Characterization and identification of differentially expressed microRNAs during the process of the peribiliary fibrosis induced by Clonorchis sinensis
Characterization and identification of differentially expressed microRNAs during the process of the peribiliary fibrosis induced by Clonorchis sinensis
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华支睾吸虫诱导胆管周围纤维化过程中差异表达microRNA的表征与鉴定
DOI：
10.1016/j.meegid.2016.06.009
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发表时间：
2016-09-01
影响因子：
3.2
通讯作者：
Zheng, Kui-Yang
中科院分区：
文献类型：
--
作者：
Yan, Chao;Shen, Li-Ping;Zheng, Kui-Yang
华支睾吸虫感染可导致胆道纤维化。MicroRNAs （miRNAs）在肝脏疾病的基因表达调控中起着重要作用。然而，可能调控中华绒螯蟹门脉纤维形成的mirna的差异表达尚未被研究。采用miRNA芯片分析不同时间点中华华家螺感染小鼠肝脏miRNAs的表达谱，并采用实时荧光定量PCR （qRT-PCR）进行验证。感染后2周、8周和16周，与感染后0周的小鼠相比，有349种mirna在感染后小鼠肝脏中差异表达，其中143种mirna下调，206种mirna上调。这些异常mirna均可能通过调控癌相关信号通路、TGF- β信号通路、MAPK信号通路、toll样受体信号通路、PI3K /AKT信号通路等参与华支睾吸虫病的病理过程，其中169个异常mirna被预测参与TGF/Smads信号通路，而TGF/Smads信号通路在华支睾吸虫引起的胆道纤维化中起重要作用。此外，miRNA-32、miRNA-34a、miRNA-125b和miRNA-497与Smad7表达呈负相关，表明这些mirna可能特异性下调Smad7表达，参与中华绒螯蟹引起的胆道纤维化的调控。本研究结果首次证实了miRNAs在中华支睾吸虫感染小鼠肝脏中存在差异表达，这些miRNAs可能在中华支睾吸虫引起的胆周纤维化调控中发挥重要作用，为华支睾吸虫病的治疗提供了可能的靶点。(C) 2016 Elsevier B.V.版权所有
Clonorchis sinensis (C. sinensis) infection can lead to biliary fibrosis. MicroRNAs (miRNAs) play important roles in regulation of genes expression in the liver diseases. However, the differential expression of miRNAs that probably regulates the portal fibrogenesis caused by C. sinensis has not yet been investigated. Hepatic miRNAs expression profiles from C. sinensis-infected mice at different time-points were analyzed by miRNA microarray and validated by quantitative real-time PCR (qRT-PCR). 349 miRNAs were differentially expressed in the liver of the C. sinensis-infected mice at 2, 8 or 16 weeks post infection (p.i.), compared with those at 0 week p.i., and there were 143 down-regulated and 206 up-regulated miRNAs among them. These all dysregulated miRNAs were potentially involved in the pathological processes of clonorchiasis by regulation of cancer-related signaling pathway, TGF-beta signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, PI3K /AKT signaling pathway, etc. 169 of these dysregulated miRNAs were predicted to be involved in the TGF/Smads signaling pathway which plays an important role in the biliary fibrosis caused by C. sinensis. Additionally, miRNA-32, miRNA-34a, miRNA-125b and miRNA-497 were negatively correlated with Smad7 expression, indicating these miRNAs may specifically down-regulate Smad7 expression and participate in regulation of biliary fibrosis caused by C. sinensis. The results of the present study for the first time demonstrated that miRNAs were differentially expressed in the liver of mice infected by C. sinensis, and these miRNAs may play important roles in regulation of peribiliary fibrosis caused by C. sinensis, which may provide possible therapeutic targets for clonorchiasis. (C) 2016 Elsevier B.V. All rights reserved.