MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression.
MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression.
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DOI：
10.4049/jimmunol.0803560
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发表时间：
2009-04-15
期刊：
影响因子：
--
通讯作者：
Rothenberg ME
中科院分区：
文献类型：
--
作者：
Lu TX;Munitz A;Rothenberg ME
变应性气道炎症的特征是基因和蛋白质表达的显著原位变化，但microRNA（miRNAs），一个新的关键mRNA调控分子家族，在这一过程中的作用尚未报道。使用高度敏感的基于微阵列的方法，我们鉴定了21种在多西环素诱导的肺特异性IL-13转基因小鼠（具有过敏性气道炎症）和对照小鼠之间具有差异表达的miRNA。特别地，我们观察到与对照小鼠相比，诱导的IL-13转基因小鼠中miR-21的过表达和miR-1的低表达。这些发现在两个独立的过敏原诱导的过敏性气道炎症模型和IL-4肺转基因小鼠中得到验证。虽然IL-13诱导的miR-21表达是IL-13受体α 1依赖性的，但过敏原诱导的miR-21表达主要不依赖于IL-13受体α 1和STAT 6介导。值得注意的是，预测算法在IL-13调节的肺转录物中鉴定了潜在的直接miR-21靶点，例如在IL-13转基因小鼠中降低的IL-12 p35 mRNA。前体-miR-21的引入剂量依赖性地抑制携带IL-12 p35的3 'UTR的报告载体的细胞表达。此外，突变IL-12 p35 3 'UTR中的miR-21结合位点消除了miR-21介导的抑制。总之，我们已经确定了过敏性气道炎症中的miRNA特征，其中包括调节IL-12的miR-21，IL-12是与T辅助细胞极化密切相关的分子。
Allergic airway inflammation is characterized by marked in situ changes in gene and protein expression, yet the role of microRNAs (miRNAs), a new family of key mRNA regulatory molecules, in this process has not yet been reported. Using a highly sensitive microarray based approach, we identified 21 miRNAs with differential expression between doxycycline-induced lung-specific IL-13 transgenic mice (with allergic airway inflammation) and control mice. In particular, we observed over-expression of miR-21 and under-expression of miR-1 in the induced IL-13 transgenic mice compared to control mice. These findings were validated in two independent models of allergen-induced allergic airway inflammation and in IL-4 lung transgenic mice. While IL-13 induced miR-21 expression was IL-13 receptor alpha 1 dependent, allergen induced miR-21 expression was mediated mainly independent of IL-13 receptor alpha 1 and STAT6. Notably, predictive algorithms identified potential direct miR-21 targets among IL-13-regulated lung transcripts such as IL-12p35 mRNA that was decreased in IL-13 transgenic mice. Introduction of pre-miR-21 dose-dependently inhibited cellular expression of a reporter vector harboring the 3’UTR of IL-12p35. Moreover, mutating miR-21 binding sites in IL-12p35 3’UTR abrogated miR-21 mediated repression. In summary, we have identified a miRNA signature in allergic airway inflammation, which includes miR-21 that modulates IL-12, a molecule germane to T helper cell polarization.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
14.9
作者：
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通讯作者：
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