Producción CyT
Revista Medicina - MICRO-RNA 21 BUT NOT MIR-155 IS DIFFERENTIALLY EXPRESSED IN THE GUT MUCOSA OF PATIENTS WITH INTESTINAL INFLAMMATORY CONDITIONS
Congreso
Autoría:
Emanuel Barbiera Romero ; Anahi Rendón Soria ; FERREYRA COMPAGNUCCI, MALENA MARÍA ; María Belén Polo ; Gustavo Correa ; Martín Yantorno ; María Victoria Mercader ; Paula Chavero ; Julio De María ; Andrés Rocca ; Alicia Sambuelli ; María Virginia Gentili ; Gabriel Gondolesi ; Guillermo Docena ; Martín Rumbo ; Cecilia Muglia ; Renata CurciarelloFecha:
2022Editorial y Lugar de Edición:
Revista MedicinaResumen *
Mucosal myofibroblasts are key stromal cells involved in IBD pathogenesis and in the CRC tumor micro-environment. Here, we aimed to study the expression of miR-21 and miR-155 in the mucosa and intestinal fibroblasts from IBD and CRC patients, as potential biomarkers to predict CRC outcome in patients with chronic intestinal inflammatory disorders. Target genes and proteins regulated by these miRNAs were also analyzed. Total RNA was obtained from mucosal explants from IBD(n=25), polyp(n=8), CRC(n=7), and healthy control (HC) patients (n=16). Intestinal fibroblast primary cultures were established from colon surgical pieces (n=10). Microvesicles were obtained from fibroblast culture supernatant by ultracentrifugation. MiR-21, miR-155, PDCD4, CBX7, KRAS transcript expression was quantified by qPCR in mucosal and cell samples. Also, TNF-α was quantified by ELISA while FAP (Fibroblast Activation Protein) expression was evaluated by immunofluorescence in biopsies. We found that miR-21 was highly expressed in inflamed biopsies compared to uninflamed mucosa (p<0.01) and to HC (p<0.01), while PDCD4 levels were decreased in IBD biopsies compared to HC (p<0.01). No differences were found for miR-155 expression, and KRAS was not detectable. MiR-21 was overexpressed in the stromal compartment of the mucosa (p<0.1) compared to the epithelial layer.At the protein level, TNF-α was increased in IBD biopsies compared to HC (21.09 vs. 6.19 pg/µg of protein, p<0.1) and FAP was highly detected in inflamed intestinal biopsies from active IBD patients, polyp and CRC samples, compared to uninflamed mucosa. Fibroblast primary cultures from IBD patients and extracellular microvesicles overexpressed miR-21 (p<0.1) and miR-155 (p<0.1), while PDCD4 was downregulated (p<0.001) compared to HC fibroblasts. Our results highlight the relevance of miRNAs and fibroblasts in gut inflammation and CRC development. MiRNAs expression pattern studies would contribute to identification of CRC biomarkers Información suministrada por el agente en SIGEVAPalabras Clave
INFLAMMATIONGUT MUCOSAmicroRNAIBD