Fibroblasts overpressing WNT2b cause impairment of intestinal mucosal barrier / 南方医科大学学报
Journal of Southern Medical University
; (12): 206-212, 2023.
Article
en Zh
| WPRIM
| ID: wpr-971516
Biblioteca responsable:
WPRO
ABSTRACT
OBJECTIVE@#To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD).@*METHODS@#Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of β-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/β-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins.@*RESULTS@#In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of β-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa.@*CONCLUSION@#Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.
Palabras clave
Texto completo:
1
Índice:
WPRIM
Asunto principal:
Glicoproteínas
/
Enfermedades Inflamatorias del Intestino
/
Medios de Cultivo Condicionados
/
Uniones Estrechas
/
Células CACO-2
/
Proteínas Wnt
/
Beta Catenina
/
Receptores Frizzled
/
Fibroblastos
/
Proteínas de Uniones Estrechas
Límite:
Animals
/
Humans
Idioma:
Zh
Revista:
Journal of Southern Medical University
Año:
2023
Tipo del documento:
Article