Allergic contact dermatitis induces upregulation of identical microRNAs in humans and mice

Allergic contact dermatitis induces upregulation of identical microRNAs in humans and mice
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DOI:
10.1111/j.1600-0536.2012.02083.x
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发表时间:
2012-11-01
期刊:
影响因子:
5.5
通讯作者:
Skov, Lone
Skov, Lone
中科院分区:
医学2区
文献类型:
--
作者:
Vennegaard, Marie T.;Bonefeld, Charlotte M.;Skov, Lone

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背景MicroRNA是短的内源性RNA分子,可以与靶mRNA的部分结合,从而抑制它们的翻译并引起转录物的加速周转或降解,从而调节基因表达。已经发现几种microRNA在特应性皮炎和银屑病中上调,表明在炎性皮肤病中的作用。然而,目前还没有关于microRNA在变应性接触性皮炎中表达的研究。目标.目的探讨microRNA在变应性接触性皮炎中的表达。方法.从对二苯基环丙烯酮(DPCP)有过敏反应的受试者中收集病变和非病变皮肤活检。通过使用强过敏原二硝基氟苯,从实验小鼠模型中收集用于分析的额外样品。从所有样品中纯化RNA,并进行锁核酸微阵列分析,然后用定量聚合酶链反应(PCR)进行验证。结果在用DPCP致敏的人中,我们发现在激发的皮肤中miR-21、miR-142- 3 p、miR-142- 5 p和miR-223显著上调。在接触性过敏小鼠模型中,相同的microRNA在小鼠皮肤中显著上调。通过定量PCR证实microRNA的上调。结论这些是表明microRNA可能参与变应性接触性皮炎发病机制的第一个结果,它们表明小鼠模型是进一步研究microRNA参与变应性接触性皮炎的有价值的工具。
Background. MicroRNAs are short, endogenous RNA molecules that can bind to parts of target mRNAs, thus inhibiting their translation and causing accelerated turnover or degradation of transcripts, thereby regulating gene expression. Several microRNAs have been found to be upregulated in atopic dermatitis and psoriasis, indicating a role in inflammatory skin diseases. However, there have been no studies on the expression of microRNAs in allergic contact dermatitis. Objectives. To investigate expression of microRNAs in allergic contact dermatitis. Methods. Lesional and non-lesional skin biopsies were collected from subjects with allergic responses to diphenylcyclopropenone (DPCP). Additional samples for profiling were collected from an experimental mouse model by use of the strong allergen dinitrofluorobenzene. RNA was purified from all samples, and locked nucleic acid microarray analysis was performed, followed by validation with quantitative polymerase chain reaction (PCR). Results. In humans sensitized with DPCP, we found significant upregulation of miR-21, miR-142-3p, miR-142-5p and miR-223 in challenged skin. The same microRNAs were significantly upregulated in the skin of mice in a mouse model of contact allergy. The upregulation of microRNA was confirmed by quantitative PCR. Conclusion. These are the first results indicating that microRNAs may be involved in the pathogenesis of allergic contact dermatitis, and they show that mouse models are valuable tools for further study of the involvement of microRNAs in allergic contact dermatitis.