Epithelial sel1L is required for the maintenance of intestinal homeostasis

Sun, Shengyi, Lourie, Rohan, Cohen, Sara B., Ji, Yewei, Goodrich, Julia K., Poole, Angela C., Ley, Ruth E., Denkers, Eric Y., McGuckin, Michael A., Long, Qiaoming, Duhamel, Gerald E., Simpson, Kenneth W. and Qi, Ling (2016) Epithelial sel1L is required for the maintenance of intestinal homeostasis. Molecular Biology of the Cell, 27 3: 483-490. doi:10.1091/mbc.E15-10-0724


Author Sun, Shengyi
Lourie, Rohan
Cohen, Sara B.
Ji, Yewei
Goodrich, Julia K.
Poole, Angela C.
Ley, Ruth E.
Denkers, Eric Y.
McGuckin, Michael A.
Long, Qiaoming
Duhamel, Gerald E.
Simpson, Kenneth W.
Qi, Ling
Title Epithelial sel1L is required for the maintenance of intestinal homeostasis
Journal name Molecular Biology of the Cell   Check publisher's open access policy
ISSN 1939-4586
1059-1524
Publication date 2016-02-01
Year available 2015
Sub-type Article (original research)
DOI 10.1091/mbc.E15-10-0724
Open Access Status DOI
Volume 27
Issue 3
Start page 483
End page 490
Total pages 8
Place of publication Bethesda, United States
Publisher American Society for Cell Biology
Collection year 2017
Language eng
Formatted abstract
Inflammatory bowel disease (IBD) is an incurable chronic idiopathic disease that drastically decreases quality of life. Endoplasmic reticulum (ER)–associated degradation (ERAD) is responsible for the clearance of misfolded proteins; however, its role in disease pathogenesis remains largely unexplored. Here we show that the expression of SEL1L and HRD1, the most conserved branch of mammalian ERAD, is significantly reduced in ileal Crohn’s disease (CD). Consistent with this observation, laboratory mice with enterocyte-specific Sel1L deficiency (Sel1LΔIEC) develop spontaneous enteritis and have increased susceptibility to Toxoplasma gondii–induced ileitis. This is associated with profound defects in Paneth cells and a disproportionate increase of Ruminococcus gnavus, a mucolytic bacterium with known association with CD. Surprisingly, whereas both ER stress sensor IRE1α and effector CHOP are activated in the small intestine of Sel1LΔIEC mice, they are not solely responsible for ERAD deficiency–associated lesions seen in the small intestine. Thus our study points to a constitutive role of Sel1L-Hrd1 ERAD in epithelial cell biology and the pathogenesis of intestinal inflammation in CD.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Health Services Publications
Mater Research Institute-UQ (MRI-UQ)
Non HERDC
 
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