PUBLICATION
Erbin exerts a protective effect against inflammatory bowel disease by suppressing autophagic cell death
- Authors
- Shen, T., Li, S., Cai, L.D., Liu, J.L., Wang, C.Y., Gan, W.J., Li, X.M., Wang, J.R., Sun, L.N., Deng, M., Liu, Y.H., Li, J.M.
- ID
- ZDB-PUB-180321-13
- Date
- 2018
- Source
- Oncotarget 9: 12035-12049 (Journal)
- Registered Authors
- Keywords
- Erbin, autophagy, cell death, inflammatory bowel disease
- MeSH Terms
- none
- PubMed
- 29552291 Full text @ Oncotarget
Citation
Shen, T., Li, S., Cai, L.D., Liu, J.L., Wang, C.Y., Gan, W.J., Li, X.M., Wang, J.R., Sun, L.N., Deng, M., Liu, Y.H., Li, J.M. (2018) Erbin exerts a protective effect against inflammatory bowel disease by suppressing autophagic cell death. Oncotarget. 9:12035-12049.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping