INVESTIGADORES
MUGLIA Cecilia Isabel
congresos y reuniones científicas
Título:
The Role of the Galectin-1 in the Pathogenesis of IBD
Autor/es:
PAPA GOBBI, R; SAMBUELLI, A.; ROCCA, A; MUGLIA C.I.; CURCIARELLO, R; RABINOVICH, G.; TOSCANO, M.; GIL, ANÍBAL; NEGREIRA, SILVIA; HUERNOS, S; CONCALVES, S; BELLICOSO, M; TIRADO, P; YANTORNO, M; IRIGIOYEN, A; DOCENA, G.
Reunión:
Congreso; Gastroenterology International Congress; 2014
Resumen:
BACKGROUND: Inflammatory bowel diseases (IBD) are multifactorial disorders characterizedby a chronic and relapsing intestinal inflammation. Galectin-1, a ubiquitous endogenouslectin, has been implicated in several chronic inflammatory disorders. AIM: We aimed toanalyze its role in the colonic mucosa of patients with Crohn′s disease (CD) and Ulcerativecolitis (UC). MATERIAL AND METHODS: Gal-1 expression was studied by qPCR, immunoblottingand histology in biopsies and resected tissues of patients with IBD (n=26) andcontrol patients (n=20). Gal-1-specific binding ligands were also analyzed by flow cytometryin lamina propria and its physiologycal role in the induction of cell death was evaluated byflow cytometry. RESULTS: We found in 21 biopsies of CD and 22 biopsies of CU that Gal-1 mRNA expression was increased in colonic inflamed areas (p<0.01). However Gal-1 proteinexpression was lower as compared to non-inflamed areas. To clarify this controversial findingwe cultured control biopsies with TNF-α (1, 5 and 10 ng/mL) and observed a doseresponseincrease in the expression and secretion of Gal-1 (p<0.05). Additionally, fibroblastsupernatants from IBD patients show the ability to cleave Gal-1 protein. Both findings couldexplain the dissociation between mRNA expression and protein secretion. Gal-1-specificbinding sites were considerably reduced in isolated lamina propria CD4 or CD8 lymphocytesfrom inflamed areas (n=11), as compared to non-inflamed areas (n=10) or control samples(n=8) (p<0.05). A consistent lower binding of PNA and C2GnT-1 expression was found inIBD samples, suggesting lower levels of asialo-core 1-O-glycans. When apoptosis was analyzedwe found that 10 ng Gal-1 increased the frequency of annexin-1-positive cells in controlpatients (n=6) (17,94% with medium and 32,94 with 10 ng Gal-1. p<0,05). Neverthelessno increased in the frequency of annexin-1-positive cells was observed in inflamed areas ofIBD patients (n=5, p=0,9647). CONCLUSIONS: In conclusion, we found a differentialexpression of Gal-1 and Gal-1-specific glycosylated ligands in biological samples of IBD.We also found that Gal-1 exerts a pro-apoptotic effect in T lymphocytes from non-inflamedareas, whereas T cells from inflamed areas are refractory to cell death. The reduced expressionof this protein in inflamed areas and the absence of Gal-1-specific sites may have relevantimplications in the survival vs cell death of mucosal T lymphocytes. This might impact inthe persistency of the inflammatory process in the affected colon.