Gastroenterology

Abstract

Inflammatory bowel disease (IBD) constitutes a substantial risk factor for colorectal cancer. Connexin 43 (Cx43) is a protein that forms gap junction (GJ) complexes involved in intercellular communication, and its expression is altered under pathological conditions, such as IBD and cancer. Recent studies have implicated epigenetic processes modulating DNA methylation in the pathogenesis of diverse inflammatory and malignant diseases. The ten-eleven translocation-2 (TET-2) enzyme catalyzes the demethylation, hence, regulating the activity of various cancer-promoting and tumor-suppressor genes. downregulating gap junctional protein Cx43, and in colon tissues from mice exposed to CBX. These results suggest that TET-2 expression levels, as well as Cx43 expression levels, are modulated in models of intestinal inflammation. We hypothesize that TET-2 may demethylate genes involved in inflammation and tumorigenesis, such as Cx43, potentially contributing to intestinal inflammation and associated carcinogenesis. reduced gap junction-mediated intercellular communication and 43 (Cx43)]. The involvement of the demethylating enzyme ten-eleven translocation-2 (TET-2) (methylcytosine dioxygenase) in the inflammatory process has motivated the investigation of Cx43 and TET-2 expression in colitis and colorectal carcinoma. In vitro and in vivo data report on the upregulation of Cx43 in inflammatory states and a downregulation of TET-2. In human samples of colon adenocarcinoma, both TET-2 and Cx43 were downregulated, potentially implicating them in the malignant transformation of inflamed intestinal tissues. transcriptional levels in colon tissues from patients with IBD[53].The present study examined the expression of Cx43 and TET-2 in an in vitro model of colon epithelium, where HT-29 cells were used in their parental state or with upregulated or knocked-out Cx43 in the presence or absence of inflammation (induced by DSS or by the addition of an inflammatory medium). A DSS-induced colitis murine model was used to describe how inflammation modulates the expression of Cx43 and TET-2. Data were then compared to Cx43 and TET-2 expression levels in tissues obtained from patients with ulcerative colitis or sporadic colorectal cancer. this that in the intestinal cell line to of In in