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

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.

• Authors: Yash A Choksi, Vishruth K Reddy, Kshipra Singh, Caitlyn W Barrett, Sarah P Short, Bobak Parang, Cody E Keating, Joshua J Thompson, Thomas G Verriere, Rachel E Brown, M Blanca Piazuelo, David M Bader, M Kay Washington, Mukul K Mittal, Thomas Brand, Alain P Gobert, Lori A Coburn, Keith T Wilson, Christopher S Williams
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 11 Issue 5 Pg. 1363-1374 (09 2018) ISSN: 1935-3456 [Electronic] United States
• PMID: 29907869 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• BVES protein, human
• Cell Adhesion Molecules
• Membrane Proteins
• Muscle Proteins
• RNA, Messenger
• Dextran Sulfate

Topics

• Adult
• Animals
• Caco-2 Cells
• Cell Adhesion Molecules
• Cell Line
• Cell Line, Tumor
• Citrobacter rodentium (pathogenicity)
• Coculture Techniques
• Colitis, Ulcerative (metabolism)
• Colon (drug effects, metabolism)
• Dextran Sulfate (pharmacology)
• Epithelial Cells (drug effects, metabolism)
• Escherichia coli (metabolism)
• Female
• HEK293 Cells
• Humans
• Intestinal Absorption (drug effects, physiology)
• Intestinal Mucosa (drug effects, metabolism)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Middle Aged
• Muscle Proteins
• Permeability (drug effects)
• RNA, Messenger (metabolism)
• Signal Transduction (drug effects, physiology)
• Tight Junctions (drug effects, metabolism)