Ricerca Progetti nazionali, regionali, internazionaliNAZIONALIPRIN 2022 PNRRNew insights into endometriosis

New insights into endometriosis pathogenesis: role of sphingosine 1-phosphate in neutrophil activation PROSPECT

Endometriosis is an invisible and neglected disease that affects roughly 10% (190 million) of reproductive age women globally. It is a chronic inflammatory/fibrotic disease defined by the presence of endometrial-like tissue outside the uterus. The etiology of endometriosis remains unclear and recently a dysregulation of immune cells has been proposed. The disease has a major impact on the patients’ quality of life, with symptoms such as heavy menstrual flow, pelvic pain, fatigue and infertility. The absence of specific non-invasive biomarkers and the requirement of surgery for a definitive diagnosis result in a diagnostic delay of 4/8 years.

Endometriosis lacks effective treatments: surgery and hormonal drugs have limited efficacy and unacceptable side effects/risks in long-term protocols and are associated with high rates of symptom recurrence. In this complex scenario, the project aims to ascertain molecular mechanisms involved in the pathogenesis of the disease in order to identify novel non-hormonal therapeutic targets. In particular, the study will focus on the role of the bioactive sphingolipid sphingosine 1-phosphate (S1P) in the interplay between neutrophil and endometriotic cells in the pathogenesis of endometriosis. Specifically, the correlation of S1P signaling dysregulation and neutrophil activation, defined by the release of neutrophil extracellular traps (NETs), and fibrosis development will be determined in endometriotic lesions from patients (Milestone 1). Moreover, in vitro experiments will be carried out to determine the molecular mechanisms implicated in the interplay between neutrophil and endometriotic cells based on S1P signaling (Milestone 2). Finally, NET and S1P levels will be evaluated in the plasma of endometriotic women and correlated with disease severity in order

to define possible new non-invasive peripheral biomarkers for the disease (Milestone 3). The research project will be developed in 2 years following well-defined steps, in close collaboration among the two Research Units.

Advancement in the identification and treatment of endometriosis is challenging, but the impact on people’s sexual and reproductive health, quality of life and overall well-being is profound. The present project will significantly improve the knowledge on the pathogenesis of endometriosis, luckily identifying new molecular markers and therapeutic targets for diagnosis, monitoring and treatment, thus reducing the social impact of this chronic disease. Indeed, since S1P antagonists have already been developed and, in some cases, used in clinics, the possible final application from the present project will be the use of new drugs for the treatment of endometriosis in a short range of time.

 

Data di avvio 30 Novembre 2023

Data di completamento 30 Novembre 2025

Total cost  € 134541

 

Progetto P20222A8HL finanziato all’interno del Bando PRIN 2022 PNRR di cui al Decreto Direttoriale n. 1409 del 14/9/2022 nell’ambito del Piano Nazionale di Ripresa e Resilienza, Missione 4 – Componente 2. Dalla Ricerca all’Impresa - Investimento 1.1 Fondo per il Programma Nazionale della Ricerca (PNR) e Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN), finanziato dall’Unione europea – NextGenerationEU – CUP B53D23024590001