18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects of microRNA-21 on the interleukin 12/signal transducer and activator of transcription 4 signaling pathway in asthmatic mice

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          To study the effect of microRNA-21 (miRNA-21) on the regulation of the interleukin 12 (IL-12)/signal transducer and activator of transcription 4 (STAT4) pathway in the lung tissue of asthmatic mice.

          Material and methods

          Forty five male C57BL/6 mice were randomly divided into three groups of 15 mice each: normal control, asthmatic model, and dexamethasone. Our mouse model of allergic asathma was established using OVA sensitization and challenge. Hematoxylin and eosin staining was performed to observe the pathological changes in lung tissue morphology. Both the total cell number and the amount of eosinophils (EOS) in the bronchoalveolar lavage fluid (BALF) were manually counted. The expression of miRNA-21 was detected by real time quantitative PCR. The expression levels of IL-12 and STAT4 in lung tissue were assayed via western blot, and immunohistochemistry was used to observe the distribution of their expression.

          Results

          The expression levels of miRNA-21 as well as the total number of BALF cells and EOS were significantly higher in the asthmatic model group than in the control or dexamethasone groups, with significantly higher amounts found in the dexamethasone group than in the control group. The expression levels of IL-12 and STAT4 proteins were lower in the asthmatic model group than in the control and dexamethasone groups, with a significantly lower expression of IL-12 and STAT4 in the dexamethasone group than in the control group.

          Conclusions

          The expression level of miRNA-21 was significantly increased and the expression level of IL-12 and STAT4 proteins was significantly decreased in allergic asthmatic mice compared with normal control mice. These findings suggest a role for miRNA-21 and the IL-12/STAT4 pathway in the development of allergic asthma.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression.

          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 overexpression of miR-21 and underexpression of miR-1 in the induced IL-13 transgenic mice compared with control mice. These findings were validated in two independent models of allergen-induced allergic airway inflammation and in IL-4 lung transgenic mice. Although IL-13-induced miR-21 expression was IL-13Ralpha1 dependent, allergen-induced miR-21 expression was mediated mainly independent of IL-13Ralpha1 and STAT6. Notably, predictive algorithms identified potential direct miR-21 targets among IL-13-regulated lung transcripts, such as IL-12p35 mRNA, which was decreased in IL-13 transgenic mice. Introduction of pre-miR-21 dose dependently inhibited cellular expression of a reporter vector harboring the 3'-untranslated region of IL-12p35. Moreover, mutating miR-21 binding sites in IL-12p35 3'-untranslated region 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 Th cell polarization.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            MicroRNA-26a targets the histone methyltransferase Enhancer of Zeste homolog 2 during myogenesis.

            MicroRNA (miRNA) are important regulators of many biological processes, but the targets for most miRNA are still poorly defined. In this study, we profiled the expression of miRNA during myogenesis, from proliferating myoblasts through to terminally differentiated myotubes. Microarray results identified six significantly differentially expressed miRNA that were more than 2-fold different in myotubes. From this list, miRNA-26a (miR-26a), an up-regulated miRNA, was further examined. Overexpression of miR-26a in murine myogenic C2C12 cells induced creatine kinase activity, an enzyme that markedly increases during myogenesis. Further, myoD and myogenin mRNA expression levels were also up-regulated. These results suggest that increased expression of miR-26a promotes myogenesis. Through a bioinformatics approach, we identified the histone methyltransferase, Enhancer of Zeste homolog 2 (Ezh2), as a potential target of miR-26a. Overexpression of miR-26a suppressed the activity of a luciferase reporter construct fused with the 3'-untranslated region of Ezh2. In addition, miR-26a overexpression decreased Ezh2 mRNA expression. These results reveal a model of regulation during myogenesis whereby the up-regulation of miR-26a acts to post-transcriptionally repress Ezh2, a known suppressor of skeletal muscle cell differentiation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis.

              IL-13 and IL-4 are central T helper 2 (Th2) cytokines in the immune system and potent activators of inflammatory responses and fibrosis during Th2 inflammation. Recent studies using Il13ra1(-/-) mice have demonstrated a critical role for IL-13 receptor (IL-13R) alpha1 in allergen-induced airway responses. However, these observations require further attention especially because IL-4 can induce similar lung pathology to IL-13, independent of IL-13, and is still present in the allergic lung. Thus, we hypothesized that IL-13Ralpha1 regulates IL-4-induced responses in the lung. To dissect the role of IL-13Ralpha1 and the type I and II IL-4Rs in experimental asthma, we examined lung pathology induced by allergen, IL-4, and IL-13 challenge in Il13ra1(-/-) mice. We report that IL-13Ralpha1 is essential for baseline IgE production, but Th2 and IgE responses to T cell-dependent antigens are IL-13Ralpha1-independent. Furthermore, we demonstrate that increased airway resistance, mucus, TGF-beta, and eotaxin(s) production, but not cellular infiltration, are critically dependent on IL-13Ralpha1. Surprisingly, our results identify a CCR3- and IL-13Ralpha1-independent pathway for lung eosinophilia. Global expression profiling of lungs from mice stimulated with allergen or IL-4 demonstrated that marker genes of alternatively activated macrophages are differentially regulated by the type I and type II IL-4R. Taken together, our data provide a comprehensive mechanistic analysis of the critical role by which IL-13Ralpha1 mediates allergic lung pathology and highlight unforeseen roles for the type II IL-4R.
                Bookmark

                Author and article information

                Journal
                Cent Eur J Immunol
                Cent Eur J Immunol
                CEJI
                Central-European Journal of Immunology
                Polish Society of Experimental and Clinical Immunology
                1426-3912
                1644-4124
                17 April 2014
                2014
                : 39
                : 1
                : 40-45
                Affiliations
                [1 ]Medical College of Lishui University, Lishui, PR China
                [2 ]The People's Hospital of Lishui City, PR China
                [3 ]Zhejiang University School of Medicine, Hangzhou, RP China
                Author notes
                Correspondence: Prof. Song-Quan Wu, Medical College of Lishui University, Xueyuan Road, Lishui City, 323000 Lishui, Zhejiang, PR China. e-mail: wusq20100429@ 123456126.com
                Article
                42121
                10.5114/ceji.2014.42121
                4439986
                b0f267c9-395e-48e2-ab69-4228c7de615d
                Copyright © Central European Journal of Immunology 2014

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 October 2013
                : 10 January 2014
                Categories
                Original Article

                allergic asthma,mirna-21,il-12,signal transducer and activator of transcription 4 (stat4)

                Comments

                Comment on this article