Objective
Activation of neutrophils by ANCA (“Anti-Neutrophil Cytoplasm Antibodies”) and subsequent endothelial cell (EC) damage is the main feature of ANCA-associated vasculitis (AAV). There is no specific treatment for AAV to date and 25% of patients evolve towards end-stage renal disease requiring dialysis and renal transplantation. While accumulating data indicate that miRNAs control major biological responses in various cell types including EC and neutrophils and are involved in the pathophysiology of several diseases, their role in AAV has been virtually unexplored. In addition, recent studies have shown that ANCA-activated neutrophils can induce EC damage through the release of microparticles, but while many studies have revealed a critical role for miRNAs secreted within microparticles in intracellular crosstalks, there is no data so far on the role of miRNAs in this process. Here, we propose to identify miRNAs deregulated in neutrophils exposed to ANCA and released in microparticles that promote EC damage in AAV. These miRNAs will be identified using TaqMan Low Density Arrays in ANCA-stimulated neutrophils in vitro and in the microparticles they release, as well as in neutrophils from patients with AAV. To assess whether these miRNAs could be used as biomarkers, their expression will also be analyzed in plasma and urine samples from AAV patients, and correlated with severity and outcome of the disease. The transfer of neutrophil-secreted miRNAs to EC will be assessed in vitro, and the function of these miRNAs in the regulation of EC responses (activation, angiogenesis) will be studied in various functional assays. While miRNAs are emerging as new therapeutic tools for several diseases, this translational study will provide the first data regarding the expression and function of neutrophil miRNAs in AAV and may therefore pave the way for novel promising miRNA-based therapeutic options in these patients.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences health sciences inflammatory diseases
- medical and health sciences clinical medicine internal medicine
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences clinical medicine nephrology
- medical and health sciences basic medicine immunology autoimmune diseases
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2014
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75654 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.