Activating transcription factor 3 promotes intestinal epithelial cell apoptosis in Crohn's disease

Intestinal epithelial cell (IEC) apoptosis plays a vital role in the pathogenesis of Crohn's disease (CD), which is an inflammatory bowel disease (IBD). Activating transcription factor 3 (ATF3) modulates apoptosis under stress via regulating the p53 pathway. However, the expression and function of ATF3 in CD are unclear. In the present study, ATF3, p53, and p53 target gene Bax expression increased in CD patients; a mouse 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced CD model; and a TNF-α-treated HT29 cell colitis model. ATF3 knockdown effectively decreased TNF-α-induced p53 and Bax expression, as well as inhibited the apoptosis of HT29 cells. Additionally, ATF3 enhanced the stability and transcription activity of p53 via interacting with p53. In summary, these data indicated that ATF3 might promote IEC apoptosis in CD via up-regulating the stability and transcription activity of p53, implying a novel molecular target for CD therapy.