Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair
Selenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. <i>SELENOW</i> expression in the human GI tract using ScRNAseq Gut Cell Atlas and Gene Expression Omnibus (GEO) dat...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/4/850 |
| _version_ | 1797606613977137152 |
|---|---|
| author | Shaneice K. Nettleford Chang Liao Sarah P. Short Randall M. Rossi Vishal Singh K. Sandeep Prabhu |
| author_facet | Shaneice K. Nettleford Chang Liao Sarah P. Short Randall M. Rossi Vishal Singh K. Sandeep Prabhu |
| author_sort | Shaneice K. Nettleford |
| collection | DOAJ |
| description | Selenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. <i>SELENOW</i> 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. <i>Selenow</i> 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. <i>Selenow</i> KO mice expressed higher colonic Tnfα, increased Tnfα<sup>+</sup> 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 <i>Selenow</i> 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. |
| first_indexed | 2024-03-11T05:17:43Z |
| format | Article |
| id | doaj.art-29b0493220d140d8acfdeca529b77d8d |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T05:17:43Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-29b0493220d140d8acfdeca529b77d8d2023-11-17T18:05:17ZengMDPI AGAntioxidants2076-39212023-04-0112485010.3390/antiox12040850Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial RepairShaneice K. Nettleford0Chang Liao1Sarah P. Short2Randall M. Rossi3Vishal Singh4K. Sandeep Prabhu5Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USADepartment of Medicine-Infectious Diseases, University of California, San Francisco, CA 94143, USADepartment of Medicine, Department of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN 37232, USAMouse Transgenic Core Facility, Huck Institute of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USADepartment of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USADepartment of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USASelenoprotein W (Selenow) is a ~9 kDa selenoprotein suggested to play a beneficial role in resolving inflammation. However, the underlying mechanisms are poorly understood. <i>SELENOW</i> 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. <i>Selenow</i> 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. <i>Selenow</i> KO mice expressed higher colonic Tnfα, increased Tnfα<sup>+</sup> 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 <i>Selenow</i> 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.https://www.mdpi.com/2076-3921/12/4/850inflammatory bowel diseaseinflammationyes-associated protein 1epidermal growth factor receptor |
| spellingShingle | Shaneice K. Nettleford Chang Liao Sarah P. Short Randall M. Rossi Vishal Singh K. Sandeep Prabhu Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair Antioxidants inflammatory bowel disease inflammation yes-associated protein 1 epidermal growth factor receptor |
| title | Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair |
| title_full | Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair |
| title_fullStr | Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair |
| title_full_unstemmed | Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair |
| title_short | Selenoprotein W Ameliorates Experimental Colitis and Promotes Intestinal Epithelial Repair |
| title_sort | selenoprotein w ameliorates experimental colitis and promotes intestinal epithelial repair |
| topic | inflammatory bowel disease inflammation yes-associated protein 1 epidermal growth factor receptor |
| url | https://www.mdpi.com/2076-3921/12/4/850 |
| work_keys_str_mv | AT shaneiceknettleford selenoproteinwamelioratesexperimentalcolitisandpromotesintestinalepithelialrepair AT changliao selenoproteinwamelioratesexperimentalcolitisandpromotesintestinalepithelialrepair AT sarahpshort selenoproteinwamelioratesexperimentalcolitisandpromotesintestinalepithelialrepair AT randallmrossi selenoproteinwamelioratesexperimentalcolitisandpromotesintestinalepithelialrepair AT vishalsingh selenoproteinwamelioratesexperimentalcolitisandpromotesintestinalepithelialrepair AT ksandeepprabhu selenoproteinwamelioratesexperimentalcolitisandpromotesintestinalepithelialrepair |