Integrative Network-based Analysis of Colonic Detoxification Gene Expression in Ulcerative Colitis According to Smoking Status.
J Crohns Colitis
; 11(4): 474-484, 2017 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-27702825
ABSTRACT
BACKGROUNDS AND AIMS:
The effect of cigarette smoking [CS] is ambivalent since smoking improves ulcerative colitis [UC] while it worsens Crohn's disease [CD]. Although this clinical relationship between inflammatory bowel disease [IBD] and tobacco is well established, only a few experimental works have investigated the effect of smoking on the colonic barrier homeostasis focusing on xenobiotic detoxification genes.METHODS:
A comprehensive and integrated comparative analysis of the global xenobiotic detoxification capacity of the normal colonic mucosa of healthy smokers [n = 8] and non-smokers [n = 9] versus the non-affected colonic mucosa of UC patients [n = 19] was performed by quantitative real-time polymerase chain reaction [qRT PCR]. The detoxification gene expression profile was analysed in CD patients [n = 18], in smoking UC patients [n = 5], and in biopsies from non-smoking UC patients cultured or not with cigarette smoke extract [n = 8].RESULTS:
Of the 244 detoxification genes investigated, 65 were dysregulated in UC patients in comparison with healthy controls or CD patients. The expression of ≥ 45/65 genes was inversed by CS in biopsies of smoking UC patients in remission and in colonic explants of UC patients exposed to cigarette smoke extract. We devised a network-based data analysis approach for differentially assessing changes in genetic interactions, allowing identification of unexpected regulatory detoxification genes that may play a major role in the beneficial effect of smoking on UC.CONCLUSIONS:
Non-inflamed colonic mucosa in UC is characterised by a specifically altered detoxification gene network, which is partially restored by tobacco. These mucosal signatures could be useful for developing new therapeutic strategies and biomarkers of drug response in UC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inativação Metabólica
/
Fumar
/
Colite Ulcerativa
/
Expressão Gênica
/
Colo
Tipo de estudo:
Observational_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Crohns Colitis
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França