Epithelial cell-specific Atg5 knockout in mice aggravates DSS-induced colitis and activates nuclear factor-kappaB signaling pathway.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic, non-specific gastrointestinal disease, characterized by relapsing intestinal inflammation and gut barrier dysfunction. Previous studies have indicated that the malfunction of autophagy is implicated in the pathogenesis of IBD. Atg5, a core autophagy protein, regulates the formation of autophagosomes; however, whether Atg5 is involved in the pathogenesis of IBD remained unclear. Here, we aimed to investigate the influence of Atg5 in the development of dextran sulfate sodium (DSS)-induced colitis in mice and explore its underlying mechanism. Atg5-/- (intestinal epithelial cell-specific Atg5 knockout) mice and WT mice were subjected to DSS-induced colitis and analyzed the colitis susceptibility. Under administration of 2.5 % DSS drinking water, Atg5-/- mice displayed a severe colitis than WT mice, as indicated by more significant weight loss, higher disease activity index (DAI) scores, more severe colonic shortening, and higher histopathological score. Atg5 deficiency led to an increased susceptibility to colitis, manifested as enhanced expression of pro-inflammatory cytokines, inhibited expression of anti-inflammatory factors, and decreased expression of intestinal tight junction/adherens junction (TJ/AJ) proteins. Mechanistically, the pathology may be caused by the activation of the NF-κB pathway. Thus, this study revealed the protective effect and molecular mechanism of the key autophagy gene Atg5 in the pathogenesis of colitis, suggesting a potential target for the treatment of IBD.