Project description
Exploring an overlooked cause of sexual dysfunction in diabetes
Diabetes not only impairs blood supply but also disrupts the nervous system in genital organs, leading to sexual dysfunction (SD) and genital tissue fibrosis. This condition affects both men and women, severely diminishing quality of life and correlating with depression and social isolation. Current treatments are insufficient, with no effective solutions for vaginal or penile fibrosis. Supported by the Marie Skłodowska-Curie Actions programme, the DISD-TG2 project investigates the role of transglutaminase-2 (TG2), an enzyme that affects vascular tone and fibrosis. Researchers hypothesise that TG2 contributes to diabetes-induced SD, and targeting it with allosteric inhibitors could improve sexual function. The project aims to develop safer, more effective treatments for diabetes-related sexual dysfunction and fibrosis.
Objective
Diabetes impairs blood supply and disrupts the integrity of the nervous system in genital organs, leading to sexual dysfunction (SD) and genital tissue fibrosis in both sexes. SD is strongly correlated with depression, reduced social well-being, and a diminished quality of life. Current therapeutic options for SD are inadequate, have important side effects, and no effective treatments exist for vaginal/penile fibrosis, underscoring an urgent need for advanced mechanistic studies to identify new therapeutic targets and develop effective and safe treatments. Transglutaminase-2 (TG2) is a multifunctional enzyme that operates in two conformations: in its open conformation, it exerts transamidase activity, which has a pro-fibrotic effect; in its closed conformation, it regulates vascular tone. It has been reported that TG2 is involved in vascular dysfunction and fibrosis, and pharmacological inhibition of TG2 improves endothelial function and shows great promise for treating fibrotic diseases. However, its role in the pathophysiology of diabetes-induced SD (DISD) remains unexplored.
We hypothesize that TG2 may play a crucial role in DISD and erectile tissue fibrosis. Promoting the closed conformation of TG2 with an allosteric reversible inhibitor could improve sexual function by enhancing vascular function and preventing fibrosis.
We will test this hypothesis by investigating: i) TG2 expression/activity in primary fibroblasts isolated from healthy rat erectile tissues and the involvement of TG2 in the fibrotic process; ii) the acute effect of TG2 inhibition on sexual function in healthy rats; and iii) the role of TG2 and the therapeutic effect of allosteric TG2 inhibitors in the rat model of DISD and vaginal/penile fibrosis. Furthermore, our project will address a significant gap in the current literature by investigating female SD, contributing to a more comprehensive understanding and management of the impact of diabetes on women’s sexual health.
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 basic medicine physiology pathophysiology
- medical and health sciences clinical medicine endocrinology diabetes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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8000 Aarhus C
Denmark
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