Decreased expression of cystathionine β-synthase exacerbates intestinal barrier injury in ulcerative colitis.

Decreased expression of cystathionine β-synthase exacerbates intestinal barrier injury in ulcerative colitis.

J Crohns Colitis. 2019 Feb 05;:

Authors: Chen S, Zuo S, Zhu J, Yue T, Bu D, Wang X, Wang P, Pan Y, Liu Y

Abstract
Background and Aims: Endogenous hydrogen sulfide (H2S) regulates multiple physiological and pathological processes in colon epithelial tissues. The current study investigated the role of cystathionine β-synthase (CBS), a major producer of H2S in colon epithelial cells, in the pathogenesis of UC-related intestinal barrier injury. The expression and DNA methylation level of CBS were investigated in inflamed and non-inflamed colon tissues collected from UC patients, and the effect of decreased CBS levels on Caco-2 monolayer barrier injury and altered status of tight junctions elicited by TNF/IFN was determined.
Methods: The expression of CBS and the methylation level of the CBS promoter were assessed in non-inflamed and inflamed colon epithelial tissue samples collected from UC patients. Barrier function, status of tight junction proteins, and activation of the NF-κB p65-mediated MLCK-P-MLC signalling pathway were further investigated in Caco-2 monolayers.
Results: Decreased expression of CBS and elevated methylation levels of the CBS promoter were observed in inflamed sites compared with in non-inflamed sites in the colon epithelial samples from UC patients. In Caco-2 monolayers, decreased expression of CBS exacerbated TNF/IFN-induced barrier injury and altered localization of tight junction proteins. Decreased expression of CBS predisposed Caco-2 monolayers to injury elicited by TNF/IFN via augmentation of the NF-κB p65-mediated MLCK-P-MLC signalling pathway.
Conclusions: Decreased expression of CBS propagates the pathogenesis of UC by exacerbating inflammation-induced intestinal barrier injury. Elevated methylation of the CBS promoter might be one of the mechanisms underlying the decreased expression of CBS in inflamed sites of colon epithelial tissues from UC patients.

PMID: 30722010 [PubMed – as supplied by publisher]

PubMed Link: https://www.ncbi.nlm.nih.gov/pubmed/30722010?dopt=Abstract