BVES is required for maintenance of colonic epithelial integrity in experimental colitis by modifying intestinal permeability.

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
Mucosal Immunol. 2018 11 (5): 1363-1374

PMID: 29907869 · PMCID: PMC6162166 · DOI:10.1038/s41385-018-0043-2

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.

MeSH Terms (26)

Adult Animals Caco-2 Cells Cell Line Cell Line, Tumor Citrobacter rodentium Coculture Techniques Colitis, Ulcerative Colon Dextran Sulfate Epithelial Cells Escherichia coli Female HEK293 Cells Humans Intestinal Absorption Intestinal Mucosa Male Membrane Proteins Mice Mice, Inbred C57BL Middle Aged Permeability RNA, Messenger Signal Transduction Tight Junctions

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