DOI: 10.1101/473397Nov 22, 2018Paper

NDRG2 Regulates Adherens Junction Integrity to Restrict Colitis and Tumorigenesis

BioRxiv : the Preprint Server for Biology
Yongzheng Majian zhang

Abstract

Objective: Paracellular barriers play an important role in the pathogenesis of IBDs, such as ulcerative colitis (UC) and Crohns disease (CD), and maintain gut homeostasis. N-myc downstream-regulated gene 2 (NDRG2) has been reported to be a tumor suppressor gene and inhibits epithelial-mesenchymal transition (EMT) and colorectal cancer metastasis. However, whether NDRG2 affects colitis initiation and colitis-associated colorectal cancer is unclear. Our study aimed to elucidate the role of NDRG2 in colitis initiation and colitis-associated colorectal cancer using an intestine-specific Ndrg2 knockout mouse model. Design: We generated intestine-specific Ndrg2 knockout mice and assessed the function of Ndrg2 in established experimental colitis and colitis-associated tumor models. Results: Intestine-specific Ndrg2 deficiency caused mild spontaneous colitis with ageing, more severe inflammation in dextran sodium sulfate (DSS) and 2,4,6-Trinitrobenzenesulfonic acid (TNBS) treated mice and enhanced pro-inflammatory cytokine levels, neutrophil and macrophage recruitment. Ndrg2 loss led to adherens junction (AJ) structure destruction via E-cadherin expression attenuation, resulting in diminished epithelial barrier function and increased i...Continue Reading

Related Concepts

Colitis
Inflammation
Inflammatory Bowel Diseases
Intestines
Snails
E-Cadherin
Ubiquitin-protein ligase
Tumor Suppressor Genes
N-Myc Protein
Mice, Knockout

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