Role of cyclooxygenase pathways in bowel fibrotic remodelling in a murine model of experimental colitis.
J Pharm Pharmacol
; 75(2): 264-275, 2023 Feb 08.
Article
em En
| MEDLINE
| ID: mdl-36477570
ABSTRACT
OBJECTIVE:
Gut fibrosis occurs under chronic inflammation. This study examined the effects of different cyclooxygenase (COX) inhibitors on fibrosis in the inflamed colon.METHODS:
Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS) in albino male Sprague-Dawley rats. After 6, 12 and 18 days, macroscopic and microscopic damage, collagen and elastic fibre content were examined. At day 6, pro-fibrotic factors (collagen I and III, hydroxyproline, fibronectin, matrix metalloproteinase-2 and -9), transforming growth factor-beta (TGF-ß) signalling [TGF-ß, Ras homolog gene family member A (RhoA), phosphorylated small mother against decapentaplegic (pSMAD)-2 and -6] and peristalsis were assessed, and the effects of indomethacin, SC-560 or celecoxib were tested. KEYFINDINGS:
Six days after DNBS administration, significant histopathological signs of fibrotic remodelling were observed in rats. At day 6, pro-fibrotic factors were up-regulated and colonic peristalsis was altered. COX inhibitors reversed the histochemical, molecular and functional changes in the fibrotic colon. COX inhibition reduced TGF-ß expression, SMAD2 phosphorylation and RhoA, and increased SMAD6 expression.CONCLUSIONS:
Colonic fibrosis is associated with altered bowel motility and induction of profibrotic factors driven by TGF-ß signalling. COX-1 and COX-2 inhibition counteracts this fibrotic remodelling by the modulation of TGF-ß/SMAD signalling, mainly via SMAD6 induction and reduction in SMAD2 phosphorylation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colite
/
Metaloproteinase 2 da Matriz
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharm Pharmacol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Itália