Abstract:
Inflammatory bowel disease (IBD) is a complex disease characterized by chronic inflammation of the gastrointestinal tract. There is evidence that IBD patients have higher propensity to develop colorectal cancer. The study of the junctional complexes is essential for a better understanding of the functional coordination between IECs and inflammatory cells in IBD, intestinal barrier function and its progression to colon cancer. On the epigenetic level, Ten-eleven translocation (TET) proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and are reported to be dysregulated in different tumors. We studied the expression of TET2 as a function of Cx43 regulation using an in vitro inflammation cell culture model, and using normal, IBD, and colon cancer human archived tissues. We documented TET2 functionality by determining the levels of 5-hmC epigenetic modification under the same conditions. Our data demonstrate that TET2 expression decreases upon an induced inflammation as well as upon the Cx43 upregulation, whereas TET2 expression increases when Cx43 is downregulated. In addition, 5-hmC levels mimic that of TET2 expression, thus reflecting TET2 functionality. The expression of TET2 and its epigenetic mark 5-hmC in Normal, IBD and colon cancer human colon tissues is highly downregulated in IBD and colon cancer human tissues when compared to Normal colon tissues.
