Descrizione del progetto
Nuove informazioni sulla patogenesi dell’infiammazione intestinale cronica
La transizione epiteliale-mesenchimale (EMT, Epithelial–Mesenchymal Transition), in cui le cellule epiteliali immobili si convertono in cellule mesenchimali migranti, è un processo che svolge un ruolo fondamentale nel corso dello sviluppo e che viene riattivato nell’ambito di determinate patologie come il cancro, in cui contribuisce alla trasformazione maligna, alla progressione e alla resistenza alla terapia. Il progetto INFLEMT, finanziato dall’UE, concentra la sua attenzione sul ruolo della EMT nella malattia infiammatoria intestinale, un disturbo cronico del tratto digerente. Nell’ambito di questo disturbo, i ricercatori studieranno la EMT e ne chiariranno l’impatto sulle cellule epiteliali intestinali nonché sullo sviluppo della fibrosi. Considerando l’elevata prevalenza della malattia infiammatoria intestinale, i risultati riveleranno informazioni importanti sulla patogenesi della malattia e potrebbero condurre a nuove strategie di trattamento.
Obiettivo
Inflammatory bowel disease (IBD) defines a group of chronic inflammatory disorders of the digestive tract, with ulcerative colitis and Crohn’s disease being its two major clinical manifestations, affecting 2.5 million people in Europe. The high prevalence of IBD in Europe and the multiple clinical challenges associated with a significant degree of unresponsiveness to anti-inflammatory therapies and development of complications requiring surgical intervention demand a deeper understanding of the cellular and molecular mechanisms underpinning IBD.
This project aims to understand the role of the process termed Epithelial–to–Mesenchymal Transition (EMT), an embryonic cellular trans-differentiation program re-launched in many pathological conditions, in the pathogenesis of IBD. EMT has in fact been detected in the inflamed intestinal mucosa and surrounding fibrotic areas of IBD patients and experimental models of colitis, however whether EMT functionally contributes to the pathogenesis of IBD is poorly understood.
The INFLEMT project aims to: 1) profile EMT in human IBD to identify its cellular features and correlation with the disease stage; 2) elucidate the impact of EMT on the integrity, functionality and regenerative capacity of the intestinal epithelial barrier; 3) explore the effects of EMT on fibrosis development and modulation of the immune response to assess its role in sustaining the chronic intestinal disease.
These objectives will be pursued by utilizing patient-derived biopsies as well as novel mouse models to manipulate EMT in the intestinal epithelium. Comprehensive analysis, including RNA-sequencing and multispectral imaging, of the involved cellular and microenvironmental components (epithelial barrier, immune cells, fibroblasts) will be performed in acute and chronic colitis settings to mechanistically configure EMT as an epithelial injury response and a major functional driver in the pathogenesis of IBD.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
20090 Pieve Emanuele
Italia