Descripción del proyecto
Nuevos conocimientos sobre la patogenia de la inflamación intestinal crónica
La transición epitelial mesenquimatosa (TEM, o EMT por sus siglas en inglés), un proceso por el que células epiteliales estáticas se convierten en células mesenquimatosas migratorias, desempeña un papel fundamental durante el desarrollo. Sin embargo, la TEM se reactiva en ciertas enfermedades, como el cáncer, lo que contribuye a la transformación maligna, la progresión y la resistencia al tratamiento. En el proyecto INFLEMT, financiado con fondos europeos, se aborda el papel de la TEM en la enfermedad inflamatoria intestinal (EII), un trastorno crónico del tubo digestivo. Sus investigadores estudiarán la TEM en la EII y dilucidarán su repercusión en las células epiteliales intestinales y en el desarrollo de fibrosis. Teniendo en cuenta la alta prevalencia de la EII, los resultados revelarán información relevante sobre la patogenia de esta enfermedad y podrían dar lugar a nuevas estrategias de tratamiento.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
20090 Pieve Emanuele
Italia