Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair

Shaneice K. Nettleford; Chang Liao; Sarah P. Short; Randall M. Rossi; Vishal Singh; K. Sandeep Prabhu

doi:10.3390/antiox12040850

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Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair

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Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair

Shaneice K. Nettleford, Chang Liao, Sarah P. Short, Randall M. Rossi, Vishal Singh and K. Sandeep Prabhu

Antioxidants, Vol.12(4), p.850

04/01/2023

DOI: 10.3390/antiox12040850

PMCID: PMC10134982

PMID: 37107231

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Abstract

Selenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. SELENOW expression in the human GI tract using ScRNAseq Gut Cell Atlas and Gene Expression Omnibus (GEO) databases revealed its expression in the small intestine and colonic epithelial, endothelial, mesenchymal, and stem cells and correlated with a protective effect in ulcerative colitis patients. Selenow KO mice treated with 4% dextran sodium sulfate (DSS) showed exacerbated acute colitis, with greater weight loss, shorter colons, and increased fecal occult blood compared to the WT counterparts. Selenow KO mice expressed higher colonic Tnfα, increased Tnfα + macrophages in the colonic lamina propria, and exhibited loss in epithelial barrier integrity and decreased zonula occludens 1 (Zo-1) expression following DSS treatment. Expression of epithelial cellular adhesion marker (EpCam), yes-associated protein 1 (Yap1), and epidermal growth factor receptor (Egfr) were decreased along with CD24lo cycling epithelial cells in Selenow KO mice. Colonic lysates and organoids confirmed a crosstalk between Egfr and Yap1 that was regulated by Selenow. Overall, our findings suggest Selenow expression is key for efficient resolution of inflammation in experimental colitis that is mediated through the regulation of Egfr and Yap1.

epidermal growth factor receptor

inflammation

inflammatory bowel disease

yes-associated protein 1

Details

Title: Subtitle: Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair
Creators: Shaneice K. Nettleford - Pennsylvania State University
Chang Liao - University of California, San Francisco
Sarah P. Short - Vanderbilt University Medical Center
Randall M. Rossi - Pennsylvania State University
Vishal Singh - Pennsylvania State University
K. Sandeep Prabhu - Pennsylvania State University
Resource Type: Journal article
Publication Details: Antioxidants, Vol.12(4), p.850
DOI: 10.3390/antiox12040850
PMID: 37107231
PMCID: PMC10134982
NLM abbreviation: Antioxidants (Basel)
ISSN: 2076-3921
eISSN: 2076-3921
Publisher: MDPI
Grant note: National Institutes of Health #0000005; PEN04771; K01DK123495 / USDA-NIFA DK 077152 / Office of Dietary Supplements
Language: English
Date published: 04/01/2023
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984420936002771

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