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H I C I SIGNED

Transcriptional and epigenetic control of tissue regenerative HB-EGF in autoimmune CNS inflammation

Total Cost €

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EC-Contrib. €

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Partnership

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 H I C I project word cloud

Explore the words cloud of the H I C I project. It provides you a very rough idea of what is the project "H I C I" about.

sclerosis    deficits    acute    ligand    inflammatory    blockade    diseases    methylation    astrocytic    promoter    autoimmune    binding    heparin    hb    transcription    receptor    animal    cns    regulation    glial    therapeutically    model    degenerative    inflammation    preliminary    neurological    cells    knock    dna    risk    patients    protective    fluid    progressive    knocking    regenerative    recover    status    destruction    exacerbated    ligands    biomarkers    serum    accumulation    egf    decreased    dnmt1    induce    disease    inhibited    hydrocarbon    nasal    chronic    mechanisms    ahr    multiple    tissue    untreatable    regeneration    modifications    explore    induction    translational    therapeutic    inhibit    mediated    methyltransferase    cerebrospinal    therapy    discovered    monitoring    worsening    stages    activation    aryl    gain    ms    led    nervous    validate    epigenetic    unknown    astrocytes    central    fail    concomitantly    sites    revealed    prevented   

Project "H I C I" data sheet

The following table provides information about the project.

Coordinator
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN 

Organization address
address: ISMANINGER STRASSE 22
city: MUENCHEN
postcode: 81675
website: http://www.med.tu.muenchen.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙499˙706 €
 EC max contribution 1˙499˙706 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-03-01   to  2025-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN DE (MUENCHEN) coordinator 1˙499˙706.00

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 Project objective

Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS), in which chronic inflammation and failure of regenerative mechanisms lead to progressive tissue destruction and accumulation of neurological deficits. Glial cells such as astrocytes induce regenerative processes in acute inflammation, but fail to inhibit tissue destruction for yet unknown reasons in chronic disease. In preliminary studies, we identified heparin-binding EGF-like growth factor (HB-EGF) in astrocytes as novel tissue protective factor. Indeed, knock-down of HB-EGF in astrocytes led to exacerbated disease and failure to recover in an animal model of MS. Promoter studies revealed induction of HB-EGF by the ligand-induced transcription factor aryl hydrocarbon receptor (AHR) in acute inflammation. However, astrocytic HB-EGF decreased in chronic stages concomitantly with progressive disease worsening. Analyses of AHR binding sites in the HB-EGF promoter revealed epigenetic modifications mediated by DNA-Methyltransferase 1 (DNMT1) in chronic inflammation, which inhibited promoter activation by AHR. Knocking down DNMT1 prevented epigenetic changes and increased HB-EGF production in chronic stages. Thus, we have discovered astrocytic HB-EGF as a novel regenerative factor and its regulation by AHR and DNMT1, which could be targeted therapeutically to enhance tissue regeneration in chronic stages. In this project, we will define the role of HB-EGF in acute and chronic autoimmune CNS inflammation (Aim 1), its regulation by AHR and DNMT1 (Aim 2), and the therapeutic value of nasal HB-EGF application or DNMT1 blockade (Aim 3). In a translational approach, we will validate AHR ligands, HB-EGF and HB-EGF promoter methylation status in serum and cerebrospinal fluid of MS patients as novel biomarkers for MS (Aim 4). These high risk/high gain studies explore novel concepts for monitoring and therapy of yet untreatable stages of MS and other degenerative diseases of the CNS.

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The information about "H I C I" are provided by the European Opendata Portal: CORDIS opendata.

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