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

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

doi:10.1038/s41385-018-0043-2

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

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

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, …

Mucosal immunology, Vol.11(5), pp.1363-1374

09/01/2018

DOI: 10.1038/s41385-018-0043-2

PMCID: PMC6162166

PMID: 29907869

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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.

Immunology

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: BVES is required for maintenance of colonic epithelial integrity in experimental colitis by modifying intestinal permeability
Creators: Yash A. Choksi - Vanderbilt University Medical Center
Vishruth K. Reddy - Vanderbilt University Medical Center
Kshipra Singh - Vanderbilt University Medical Center
Caitlyn W. Barrett - Vanderbilt University Medical Center
Sarah P. Short - Vanderbilt University Medical Center
Bobak Parang - Vanderbilt University Medical Center
Cody E. Keating - Vanderbilt University Medical Center
Joshua J. Thompson - Vanderbilt University Medical Center
Thomas G. Verriere - Vanderbilt University Medical Center
Rachel E. Brown - Vanderbilt University Medical Center
M. Blanca Piazuelo - Vanderbilt University Medical Center
David M. Bader - Vanderbilt University
M. Kay Washington - Vanderbilt University
Mukul K. Mittal - Vanderbilt University Medical Center
Thomas Brand - Imperial College London
Alain P. Gobert - Vanderbilt University Medical Center
Lori A. Coburn - Vanderbilt University Medical Center
Keith T. Wilson - Vanderbilt University Medical Center
Christopher S. Williams - Vanderbilt University Medical Center
Resource Type: Journal article
Publication Details: Mucosal immunology, Vol.11(5), pp.1363-1374
DOI: 10.1038/s41385-018-0043-2
PMID: 29907869
PMCID: PMC6162166
NLM abbreviation: Mucosal Immunol
ISSN: 1933-0219
eISSN: 1935-3456
Publisher: Springer Nature
Number of pages: 12
Grant note: 116552 / American Cancer Society 1I01 BX001426; 2I01 BX001453 / Office of Medical Research, Department of Veterans Affairs; US Department of Veterans Affairs 1IK2 BX002126 / Office of Medical Research, Department of Veterans Affairs (Career Development Award) F31CA167920; P30CA068485; P50CA095103 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) UL1TR002243; UL1TR000445 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) R01DK099204; K08DK080221; 5T32DK00767322; 1F30DK103498; T32GM07347; R01AT004821; P50CA095103; T32GM007347; 1F30DK096718; 1F31CA167920; 5F32 DK108492; P30DK058404 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA I01BX001426; I01BX001453; IK2BX002126 / Veterans Affairs; US Department of Veterans Affairs R01AT004821 / National Center for Complementary & Integrative Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA068485 / National Cancer Institute Cancer Center Support Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CA68485; DK20593; DK58404; DK59637; EY08126 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA UL1TR000445 / CTSA award from the National Center for Advancing Translational Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) S10OD021630 / OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA F30DK103498; P60DK020593; F30DK096718; F32DK108492; U2CDK059637; U24DK059637; T32DK007673; K08DK080221; R01DK099204; P30DK058404; P30DK020593 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) T32GM007347 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) P30EY008126 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) MR/J010383/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Language: English
Date published: 09/01/2018
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984420837802771

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