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Publication
BVES is required for maintenance of colonic epithelial integrity in experimental
colitis by modifying intestinal permeability.
Authors Choksi YA, Reddy VK, Singh K, Barrett CW, Short SP, Parang B, Keating CE,
Thompson JJ, Verriere TG, Brown RE, Piazuelo MB, Bader DM, Washington MK, Mittal
MK, Brand T, Gobert AP, Coburn LA, Wilson KT, Williams CS
Submitted By Submitted Externally on 11/5/2018
Status Published
Journal Mucosal immunology
Year 2018
Date Published 9/1/2018
Volume : Pages 11 : 1363 - 1374
PubMed Reference 29907869
Abstract Blood vessel epicardial substance (BVES), or POPDC1, is a tight
junction-associated transmembrane protein that modulates
epithelial-to-mesenchymal transition (EMT) via junctional signaling pathways.
There have been no in vivo studies investigating the role of BVES in colitis. We
hypothesized that BVES is critical for maintaining colonic epithelial integrity.
At baseline, Bves-/- mouse colons demonstrate increased crypt height, elevated
proliferation, decreased apoptosis, altered intestinal lineage allocation, and
dysregulation of tight junctions with functional deficits in permeability and
altered intestinal immunity. Bves-/- mice inoculated with Citrobacter rodentium
had greater colonic injury, increased colonic and mesenteric lymph node
bacterial colonization, and altered immune responses after infection. We propose
that increased bacterial colonization and translocation result in amplified
immune responses and worsened injury. Similarly, dextran sodium sulfate (DSS)
treatment resulted in greater histologic injury in Bves-/- mice. Two different
human cell lines (Caco2 and HEK293Ts) co-cultured with enteropathogenic E. coli
showed increased attaching/effacing lesions in the absence of BVES. Finally,
BVES mRNA levels were reduced in human ulcerative colitis (UC) biopsy specimens.
Collectively, these studies suggest that BVES plays a protective role both in
ulcerative and infectious colitis and identify BVES as a critical protector of
colonic mucosal integrity.




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