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nature portfolio privacy policy advertising nature myocyte-enriched calcineurin-interacting protein egfp-myc-irf8 recombinant plasmid yield canfatc1-cre-tg mice 0/ reprints produce cardiac-specific irf8-tg linearized α-mhc-irf8 plasmid mem-cre-tg mice served replication-defective adenoviral vectors wayne bond lau c-terminal flag-tagged canfatc1 α-myosin heavy chain confocal laser-scanning microscope adnfatc1-luc/bnp-luc/mcip1 ab-operated irf8-tg mice calcineurin inhibitors cabin1/cain ab-induced cardiac hypertrophy β-myosin heavy chain human dendritic-cell immunodeficiency lv end-diastolic dimension lv end-systolic dimension generate egfp-myc-irf8δ200–377 induce cre-dependent recombination full size image irf8 deficiency aggravates diluted media cytosolic pattern-recognition receptors nox2 mediate tcf/lef l-type ca2+ channel author correspondence calcineurin-dependent transcriptional pathway calcineurin/nfat coupling participates n-terminal hemagglutinin-tagged ab-induced nuclear translocation consensus sequence-binding protein cardiac-specific canfatc1-tg m-mode images derived social media rna-protein scaffold complex glutathione-sepharose 4b beads nfat-mediated transcriptional activation24 serum-free dmem/f12 nramp1-mediated innate resistance pure c57bl/6j background real-time pcr assays xue-hai zhu psi-egfp-myc-c1

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         description:Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)-induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits the hypertrophic response. Inhibition of NFATc1 ameliorates the cardiac abnormalities in IRF8−/− mice after AB. In contrast, constitutive activation of NFATc1 nullifies the protective effects of IRF8 on cardiac hypertrophy in IRF8-overexpressing mice. Our results indicate that IRF8 is a potential therapeutic target in pathological cardiac hypertrophy. The transcription factor interferon regulatory factor 8 (IRF8) is known to regulate differentiation and function of immune cells. Here the authors show that IRF8 is upregulated in the hypertrophic heart in humans and mice, where it suppresses cardiac remodelling by inhibiting calcineurin signalling.
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      headline:IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling
      description:Interferon regulatory factor 8 (IRF8) is known to affect the innate immune response, for example, by regulating the differentiation and function of immune cells. However, whether IRF8 can influence cardiac hypertrophy is unknown. Here we show that IRF8 levels are decreased in human dilated/hypertrophic cardiomyopathic hearts and in murine hypertrophic hearts. Mice overexpressing Irf8 specifically in the heart are resistant to aortic banding (AB)-induced cardiac hypertrophy, whereas mice lacking IRF8 either globally or specifically in cardiomyocytes develop an aggravated phenotype induced by pressure overload. Mechanistically, we show that IRF8 directly interacts with NFATc1 to prevent NFATc1 translocation and thus inhibits the hypertrophic response. Inhibition of NFATc1 ameliorates the cardiac abnormalities in IRF8−/− mice after AB. In contrast, constitutive activation of NFATc1 nullifies the protective effects of IRF8 on cardiac hypertrophy in IRF8-overexpressing mice. Our results indicate that IRF8 is a potential therapeutic target in pathological cardiac hypertrophy. The transcription factor interferon regulatory factor 8 (IRF8) is known to regulate differentiation and function of immune cells. Here the authors show that IRF8 is upregulated in the hypertrophic heart in humans and mice, where it suppresses cardiac remodelling by inhibiting calcineurin signalling.
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      name:Ding-Sheng Jiang
      affiliation:
            name:Renmin Hospital of Wuhan University
            address:
               name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
            name:Cardiovascular Research Institute of Wuhan University
            address:
               name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Xiang Wei
      affiliation:
            name:Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Xiao-Fei Zhang
      affiliation:
            name:College of Life Sciences, Wuhan University
            address:
               name:College of Life Sciences, Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Yu Liu
      affiliation:
            name:Renmin Hospital of Wuhan University
            address:
               name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
            name:Cardiovascular Research Institute of Wuhan University
            address:
               name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Yan Zhang
      affiliation:
            name:Renmin Hospital of Wuhan University
            address:
               name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
            name:Cardiovascular Research Institute of Wuhan University
            address:
               name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Ke Chen
      affiliation:
            name:College of Life Sciences, Wuhan University
            address:
               name:College of Life Sciences, Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Lu Gao
      affiliation:
            name:Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
               type:PostalAddress
            type:Organization
      name:Heng Zhou
      affiliation:
            name:Renmin Hospital of Wuhan University
            address:
               name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
            name:Cardiovascular Research Institute of Wuhan University
            address:
               name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Xue-Hai Zhu
      affiliation:
            name:Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
            address:
               name:Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Peter P. Liu
      affiliation:
            name:University of Ottawa Heart Institute
            address:
               name:University of Ottawa Heart Institute, Ottawa, Canada
               type:PostalAddress
            type:Organization
      name:Wayne Bond Lau
      affiliation:
            name:Thomas Jefferson University
            address:
               name:Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, USA
               type:PostalAddress
            type:Organization
      name:Xinliang Ma
      affiliation:
            name:Thomas Jefferson University
            address:
               name:Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, USA
               type:PostalAddress
            type:Organization
      name:Yunzeng Zou
      affiliation:
            name:Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University
            address:
               name:Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
               type:PostalAddress
            type:Organization
      name:Xiao-Dong Zhang
      affiliation:
            name:College of Life Sciences, Wuhan University
            address:
               name:College of Life Sciences, Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
      name:Guo-Chang Fan
      affiliation:
            name:University of Cincinnati
            address:
               name:Department of Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati, USA
               type:PostalAddress
            type:Organization
      name:Hongliang Li
      affiliation:
            name:Renmin Hospital of Wuhan University
            address:
               name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
            name:Cardiovascular Research Institute of Wuhan University
            address:
               name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
      name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
      name:Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:College of Life Sciences, Wuhan University, Wuhan, China
      name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
      name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
      name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
      name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
      name:College of Life Sciences, Wuhan University, Wuhan, China
      name:Department of Cardiology, Institute of Cardiovascular Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
      name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
      name:Cardiovascular Research Institute of Wuhan University, Wuhan, China
      name:Department of Thoracic and Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
      name:University of Ottawa Heart Institute, Ottawa, Canada
      name:Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, USA
      name:Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, USA
      name:Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
      name:College of Life Sciences, Wuhan University, Wuhan, China
      name:Department of Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati, USA
      name:Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
      name:Cardiovascular Research Institute of Wuhan University, Wuhan, China

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• pdns5.ultradns.info
• pdns6.ultradns.co.uk

CDN Services {📦}

• Crossref