Objective
Delayed graft function (DGF) after kidney transplantation represents the main risk factor for allograft loss. While DGF occurs rarely after living donor transplantation, about 25% of deceased donor kidney recipients develop DGF and require dialysis within the first week after transplantation. Various molecular mechanisms have been elucidated. Pro-inflammatory response after brain death and ischemic reperfusion injury are significant factors contributing to development of DGF. Nevertheless, prevention of DGF after transplantation is desirable but still not feasible.
MicroRNAs (miRNAs) are a class of small non-coding 18 to 24 nucleotide-long RNAs involved in the regulation of diverse cellular functions and in the pathogenesis of DGF. One of the most appealing properties of miRNAs as therapeutic agents is their ability to target multiple molecules, making them extremely efficient in regulating distinct biological cell processes relevant in specific diseases. One of their members, miR-182 is strongest increased during acute renal transplant failure. miR-182 regulates approx. 50% of significantly deregulated genes in renal allograft biopsies developing DGF within the first week after transplantation. Furthermore the inhibition of miR-182 showed anti-inflammatory properties over the target gene FOXO1.
Aims:
1. We will investigate whether the inhibition of miR-182 will revert transcriptional activation of genes involved in DGF in the rat donor kidney
2. To elucidate the efficacy of miR-182 antisense in preventing the incidence and duration of postischemic DGF in a rat model.
3. The third aim is to test the proposed treatment in human deceased donor kidneys, which are declined for transplantation. Machine perfusion technique (lifeport®) will be used to apply the drug into the donor kidneys ex vivo.
This study translates recent knowledge on the molecular mechanisms of DGF into a potentially applicable prophylactic intervention.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics RNA
- medical and health sciences clinical medicine transplantation
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IOF
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Funding Scheme
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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.
Coordinator
1090 Wien
Austria
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.