1. Inflammatory Bowel Disease Susceptibility Gene C1ORF106 Regulates Intestinal Epithelial Permeability.
- Author
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Manzanillo P, Mouchess M, Ota N, Dai B, Ichikawa R, Wuster A, Haley B, Alvarado G, Kwon Y, Caothien R, Roose-Girma M, Warming S, McKenzie BS, Keir ME, Scherl A, Ouyang W, and Yi T
- Subjects
- Animals, Caco-2 Cells, Carrier Proteins metabolism, Clustered Regularly Interspaced Short Palindromic Repeats genetics, Epithelial Cells metabolism, GTPase-Activating Proteins metabolism, Guanine Nucleotide Exchange Factors metabolism, HEK293 Cells, Humans, Inflammatory Bowel Diseases metabolism, Inflammatory Bowel Diseases pathology, Inflammatory Bowel Diseases therapy, Mice, Mice, Inbred C57BL, Mice, Knockout, Permeability, Receptors, Cytoplasmic and Nuclear metabolism, Tight Junctions genetics, Tight Junctions metabolism, Tumor Necrosis Factor-alpha genetics, Carrier Proteins genetics, Inflammatory Bowel Diseases genetics, Intestinal Mucosa metabolism, Intestinal Mucosa pathology
- Abstract
Intestinal epithelial cells form a physical barrier that is tightly regulated to control intestinal permeability. Proinflammatory cytokines, such as TNF-α, increase epithelial permeability through disruption of epithelial junctions. The regulation of the epithelial barrier in inflammatory gastrointestinal disease remains to be fully characterized. In this article, we show that the human inflammatory bowel disease genetic susceptibility gene C1ORF106 plays a key role in regulating gut epithelial permeability. C1ORF106 directly interacts with cytohesins to maintain functional epithelial cell junctions. C1orf106 -deficient mice are hypersensitive to TNF-α-induced increase in epithelial permeability, and this is associated with increased diarrhea. This study identifies C1ORF106 as an epithelial cell junction protein, and the loss of C1ORF106 augments TNF-α-induced intestinal epithelial leakage and diarrhea that may play a critical role in the development of inflammatory bowel disease., (Copyright © 2018 The Authors.)
- Published
- 2018
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