Erbin exerts a protective effect against inflammatory bowel disease by suppressing autophagic cell death
Metrics: HTML 1171 views | ?
Tong Shen1, Shi Li1, Ling-Dong Cai1, Jing-Lin Liu1, Chu-Yi Wang1, Wen-Juan Gan1, Xiu-Ming Li1, Jing-Ru Wang1, Li-Na Sun1, Min Deng1, Yu-Hong Liu2 and Jian-Ming Li1
1Department of Pathology, Soochow University Medical School, Suzhou 215123, People’s Republic of China
2Department of Pathology, Baoan Hospital, Southern Medical University, Shenzhen 518101, People’s Republic of China
Jian-Ming Li, email: email@example.com
Keywords: Erbin; inflammatory bowel disease; autophagy; cell death
Received: September 15, 2017 Accepted: November 16, 2017 Published: January 04, 2018
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.