A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells.
A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells.
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DOI：
10.1371/journal.pone.0111659
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sanchez-Elsner T
中科院分区：
文献类型：
--
作者：
Martinez-Nunez RT;Bondanese VP;Louafi F;Francisco-Garcia AS;Rupani H;Bedke N;Holgate S;Howarth PH;Davies DE;Sanchez-Elsner T
MicroRNAs是调节基因表达的短链非编码单链rna。虽然人们对单个microrna的作用了解甚多，但现在有越来越多的证据表明，它们可以在合作网络中发挥作用。众所周知，microrna在许多疾病中失调，并影响参与病理的途径。我们使用哮喘作为疾病模型来研究microRNA网络的失调。哮喘是一种以支气管高反应性和气道重构为特征的气道慢性炎症性疾病。气道上皮是哮喘病理的主要因素，已被证明产生过量的炎症和促重建细胞因子，如TGF-β、IL-6和IL-8，以及缺乏抗病毒干扰素。在进行microRNA阵列后，我们发现与健康供体细胞相比，哮喘支气管上皮细胞中的microRNA -18a、-27a、-128和-155下调。有趣的是，这些microrna在计算机上被预测靶向TGF-β、IL-6、IL-8和干扰素通路的几个组成部分。控制支气管上皮细胞中单个microrna的水平对这些途径都没有影响。重要的是，microrna网络miR-18a、-27a、-128和-155的敲低导致IL-8和IL-6表达显著增加。有趣的是，尽管有很强的计算机预测，下调microrna库对TGF-β和干扰素途径没有影响。总之，利用生物信息学和实验工具，我们发现了microRNA失调在哮喘中控制IL-6和IL-8表达的高度相关的潜在作用。我们的研究结果表明，microrna可能根据其他microrna的存在而具有不同的作用。因此，在研究疾病时，考虑到与其他microRNA的相互作用，应该在相关的细胞背景下实验证实对microRNA功能的计算机分析的解释。
MicroRNAs are short non-coding single stranded RNAs that regulate gene expression. While much is known about the effects of individual microRNAs, there is now growing evidence that they can work in co-operative networks. MicroRNAs are known to be dysregulated in many diseases and affect pathways involved in the pathology. We investigated dysregulation of microRNA networks using asthma as the disease model. Asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness and airway remodelling. The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-β, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons. After performing microRNA arrays, we found that microRNAs -18a, -27a, -128 and -155 are down-regulated in asthmatic bronchial epithelial cells, compared to cells from healthy donors. Interestingly, these microRNAs are predicted in silico to target several components of the TGF-β, IL-6, IL-8 and interferons pathways. Manipulation of the levels of individual microRNAs in bronchial epithelial cells did not have an effect on any of these pathways. Importantly, knock-down of the network of microRNAs miR-18a, -27a, -128 and -155 led to a significant increase of IL-8 and IL-6 expression. Interestingly, despite strong in silico predictions, down-regulation of the pool of microRNAs did not have an effect on the TGF-β and Interferon pathways. In conclusion, using both bioinformatics and experimental tools we found a highly relevant potential role for microRNA dysregulation in the control of IL-6 and IL-8 expression in asthma. Our results suggest that microRNAs may have different roles depending on the presence of other microRNAs. Thus, interpretation of in silico analysis of microRNA function should be confirmed experimentally in the relevant cellular context taking into account interactions with other microRNAs when studying disease.
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影响因子：
15.9
作者：
Lanone, S;Zheng, T;Elias, JA
通讯作者：
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影响因子：
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DOI：
10.1164/rccm.200806-992oc
发表时间：
2009-06-01
影响因子：
24.7
作者：
Fukuyama, Satoru;Nakano, Takako;Inoue, Hiromasa
通讯作者：
Inoue, Hiromasa
影响因子：
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作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
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