Role of RASSF1A in intestinal inflammation
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Abstract
Ras association domain family 1 A (RASSF1A) is an important tumor suppressor, which expression is frequently lost in various cancers due to promoter hypermethylation. Chronic inflammation, such as inflammatory bowel disease (IBD), can increase the risk of developing cancer. Rassf1a conventional knockout studies suggest its essential role in protection against dextran sulphate sodium (DSS)-induced colitis. In this study, we further explored the role of Rassf1a in intestinal inflammation by utilizing an intestinal epithelial cell (IEC) specific knockout (Rassf1aIEC-KO) mouse model. We found that the Rassf1aIEC-KO mice are more susceptible to DSS-induced colitis. Central to the pro-inflammatory signaling is the nuclear factor kappa B (NF-κB) transcription factor. We observed increased NF-κB DNA-binding activity in bone marrow cells and crypt cells in the Rassf1aIEC-KO mice. Our investigation demonstrates that the intestinal epithelial expression of Rassf1a is essential to protect the mice from DSS-induced intestinal inflammation, through the negative regulation of NF-κB activity.