Paracellular barrier function plays important role in pathogenesis of IBDs,including UC and Crohns disease(CD),and maintain the gut homeo-mstyacs diosw.n Nstream-regulated gene 2(NDRG2)has been reported to be a tumor suppressor candidate and suppressed epithelial-mesenchymal transition(EMT)via modulating expression of E-cadherin in colitisassociated cancer(CAC).However,it is not clear whether NDRG2 affects the colitis initiation.Our study aimed to elucidate the role of NDRG2 in epithelial barrier function and the colitis initiation.We generated intestine-specific knock-out mice of Ndrg2 and assessed its function in established experimental models of colitis.In mice,intestine-specific deficiency of Ndrg2 caused more severe inflammation in dextran sodium sulfate(DSS)induced colitis,and increased the levels of proinflammatory cytokines and the recruitment of neutrophils and macrophage.Furthermore,the absence of Ndrg2 lead to destruction of adherens junctions(AJs)via attenuation of E-cadherin,thus wrecked the epithelial barrier function and enhanced the permeability.In human UC cases,levels of NDRG2 was negatively associated with the recruitment of CD68+macrophage and positively associated with the expression of E-cadherin.In conclusion,these findings suggest that Ndrg2 plays important role in function of colonic epithelial barrier and modulates the gut homeostasis,and absence of Ndrg2 causes colitis initiation.