Producción CyT
Congreso
Autoría
Anahi Rendón Soria
;
Emanuel Barbiera Romero
;
Antonia Dominguez
;
FERREYRA COMPAGNUCCI, MALENA MARÍA
;
Alan Adamzcyk
;
Matias Ostrowski
;
Emanuel Llanquiman
;
Andrés Rocca
;
Alicia Sambuelli
;
María Belén Saracho
;
Santiago Brayer
;
Karina Collia
;
María Virginia Gentilini
;
Martín Rumbo
;
Guillermo Docena
;
Luis Diambra
;
Marjorie De La Fuente
;
Glauben Landskron Ramos
;
Cecilia Muglia
;
Renata Curciarello
Fecha
2024
Editorial y Lugar de Edición
SAI-ALACI-AINCA
ISSN
978-950-34-2435-3
Resumen
Información suministrada por el agente en
SIGEVA
Fibroblasts are key stromal cells in Inflammatory Bowel Disease (IBD) contributing to fibrosis andcolorectal cancer (CRC) development. Fibroblast activation protein (FAP) and microRNA-21 (miR-21) are markedly increased in several tumours. We aimed to explore FAP and miR-21 in fibroblastsfrom inflamed colonic mucosa to understand their potential contribution to tissue damage. Colonicbiopsies and surgical samples were taken from IBD(n=40), CRC(n=8) and healthy individuals(HC)(n=4) and fibroblast ...
Fibroblasts are key stromal cells in Inflammatory Bowel Disease (IBD) contributing to fibrosis andcolorectal cancer (CRC) development. Fibroblast activation protein (FAP) and microRNA-21 (miR-21) are markedly increased in several tumours. We aimed to explore FAP and miR-21 in fibroblastsfrom inflamed colonic mucosa to understand their potential contribution to tissue damage. Colonicbiopsies and surgical samples were taken from IBD(n=40), CRC(n=8) and healthy individuals(HC)(n=4) and fibroblast primary cultures were established. FAP and α-SMA were evaluated byimmunofluorescence (IF) and immunohistochemistry using tissue microarrays. MiR-21, FAP andACTA2 were quantified by qPCR in biopsies.Exosomes were enriched from fibroblast culture supernatants by ultracentrifugation (visualisedby atomic force microscopy and western blot), and miR-21 expression was analysed. In vitroinduction of FAP was evaluated in fibroblasts by IF, after stimulation with hrTGF-β or exosomalfractions. RNA samples from fibroblast lines were used for paired end RNA-seq. Raw sequencingreads were trimmed and then clean reads were mapped to the reference genome using HISAT2.Gene expression levels were estimated using Stringtie software with default settings. Differential gene expression analysis was performed using DESeq2 with default settings. MiR-21, FAP and ACTA2 were overexpressed the in inflamed mucosa compared with HC and non-inflamed mucosa from IBD and CRC patients (**p<0,01, ***p<0,001, respectively). Both proteins were increased in the stroma of inflamed areas from the same patient samples (*p<0,05). hrTGF-β and miR-21-rich-exosomal fractions induced FAP expression in fibroblast primary cultures in vitro incomparison with unstimulated fibroblast (mean ± SEM; *p<0,05). MiR-21 overexpression in chronic inflamed mucosa may induce fibroblasts activation pathways, contributing to tissue remodelling and damage. Unveiling the role of miRNAs and proteins in IBD and CRC development, may improve preventiveand therapeutic strategies
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Palabras Clave
MICRORNAFIBROSISINFLAMMATORY BOWEL DISEASE