Erbin exerts a protective effect against inflammatory bowel disease by suppressing autophagic cell death

// Tong Shen 1 , Shi Li 1 , Ling-Dong Cai 1 , Jing-Lin Liu 1 , Chu-Yi Wang 1 , Wen-Juan Gan 1 , Xiu-Ming Li 1 , Jing-Ru Wang 1 , Li-Na Sun 1 , Min Deng 1 , Yu-Hong Liu 2 and Jian-Ming Li 1 1 Department of Pathology, Soochow University Medical School, Suzhou 215123, People’s Republic of China 2 Department of Pathology, Baoan Hospital, Southern Medical University, Shenzhen 518101, People’s Republic of China Correspondence to: Jian-Ming Li, email: jianmingli@suda.edu.cn Keywords: Erbin; inflammatory bowel disease; autophagy; cell death Received: September 15, 2017      Accepted: November 16, 2017      Published: January 04, 2018 ABSTRACT The pathogenesis and key functional molecules involved in inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) remain unclear. Here, we reported that Erbin, a protein required for the polarity of epithelial cells, is conserved across species and highly expressed in the intestinal mucosa in mice and zebrafish. Pathologically, Erbin expression in the intestinal mucosa was significantly decreased in DSS induced acute colitis mice, IL-10 deficient mice and clinical biopsy specimens from patients with ulcerative colitis. Moreover, Erbin deficient mice are more susceptible to experimental colitis, exhibiting more severe intestinal barrier disruption, with increased histological scores and excessive production of proinflammatory cytokines. Mechanistically, Erbin deficiency or knockdown significantly exacerbated activation of autophagic program and autophagic cell death in vivo and in vitro . And, inhibition of autophagy by Chloroquine attenuates excessive inflammatory response in the DSS-induced colitis mouse model of Erbin deletion. Generally, our study uncovers a crucial role of Erbin in autophagic cell death and IBD, giving rise to a new strategy for IBD therapy by inhibiting excessive activation of autophagy and autophagic cell death.