MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets.
MicroRNAs profiling in murine models of acute and chronic asthma: a relationship with mRNAs targets.
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DOI：
10.1371/journal.pone.0016509
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发表时间：
2011-01-28
期刊：
影响因子：
3.7
通讯作者：
Colige A
中科院分区：
文献类型：
--
作者：
Garbacki N;Di Valentin E;Huynh-Thu VA;Geurts P;Irrthum A;Crahay C;Arnould T;Deroanne C;Piette J;Cataldo D;Colige A
MiRNAs现在被认为是基因表达的关键调控元件。尽管它们与许多人类疾病有关，但它们在急性和慢性哮喘中的作用以及它们与肺重塑的关系从未得到彻底的研究。为了建立小鼠肺组织中miRNAs的表达谱，用卵清蛋白模拟急性、中度和慢性人类哮喘进行致敏和激发。用基因芯片分析肺组织中miRNAs的水平，并进行电子计算机分析，以确定潜在的mRNA靶点，并指出由miRNA依赖的机制调控的信号通路和生物学过程。在短期、中期和长期攻击中，分别有58、66和75个miRNAs被显著调制。MMU-miR-146b、-223、-29b、-29c、-483、-574-5p、-672和-690与潜在的信使核糖核酸靶标的表达呈负相关，在哮喘发病机制中具有积极意义。通过在人肺成纤维细胞(WI26)中共转染合成的miRNAs和含有荧光素酶编码序列的工程化表达载体，进行了功能验证分析，其中包括各种潜在的mRNA靶标的3‘UTR端。生物信息学分析发现，miRNA与几个信号通路有关，如基质金属蛋白酶、炎症反应和转化生长因子-β信号，以及包括细胞凋亡和炎症在内的生物过程。这项研究强调了特定的miRNAs可能参与哮喘疾病，并可能成为识别生物标志物和揭示哮喘发病机制的宝贵资源。
miRNAs are now recognized as key regulator elements in gene expression. Although they have been associated with a number of human diseases, their implication in acute and chronic asthma and their association with lung remodelling have never been thoroughly investigated. In order to establish a miRNAs expression profile in lung tissue, mice were sensitized and challenged with ovalbumin mimicking acute, intermediate and chronic human asthma. Levels of lung miRNAs were profiled by microarray and in silico analyses were performed to identify potential mRNA targets and to point out signalling pathways and biological processes regulated by miRNA-dependent mechanisms. Fifty-eight, 66 and 75 miRNAs were found to be significantly modulated at short-, intermediate- and long-term challenge, respectively. Inverse correlation with the expression of potential mRNA targets identified mmu-miR-146b, -223, -29b, -29c, -483, -574-5p, -672 and -690 as the best candidates for an active implication in asthma pathogenesis. A functional validation assay was performed by cotransfecting in human lung fibroblasts (WI26) synthetic miRNAs and engineered expression constructs containing the coding sequence of luciferase upstream of the 3′UTR of various potential mRNA targets. The bioinformatics analysis identified miRNA-linked regulation of several signalling pathways, as matrix metalloproteinases, inflammatory response and TGF-β signalling, and biological processes, including apoptosis and inflammation. This study highlights that specific miRNAs are likely to be involved in asthma disease and could represent a valuable resource both for biological makers identification and for unveiling mechanisms underlying the pathogenesis of asthma.
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DOI：
10.1152/ajplung.90367.2008
发表时间：
2009-02-01
影响因子：
4.9
作者：
Di Valentin, Emmanuel;Crahay, Celine;Cataldo, Didier
通讯作者：
Cataldo, Didier
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
30.8
作者：
Cullen, Bryan R.
通讯作者：
Cullen, Bryan R.
影响因子：
3.1
作者：
Callis, Thomas E.;Chen, Jian-Fu;Wan, Da-Zhi
通讯作者：
Wan, Da-Zhi
DOI：
10.1016/j.jaci.2007.10.028
发表时间：
2008-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brightling C;Berry M;Amrani Y
通讯作者：
Amrani Y