| http://purl.uniprot.org/citations/25919700 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25919700 | http://www.w3.org/2000/01/rdf-schema#comment | "Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD."xsd:string |
| http://purl.uniprot.org/citations/25919700 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0125490"xsd:string |
| http://purl.uniprot.org/citations/25919700 | http://purl.uniprot.org/core/author | "Chen P."xsd:string |
| http://purl.uniprot.org/citations/25919700 | http://purl.uniprot.org/core/author | "Li Y.C."xsd:string |
| http://purl.uniprot.org/citations/25919700 | http://purl.uniprot.org/core/author | "Toback F.G."xsd:string |
| http://purl.uniprot.org/citations/25919700 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25919700 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/25919700 | http://purl.uniprot.org/core/pages | "e0125490"xsd:string |
| http://purl.uniprot.org/citations/25919700 | http://purl.uniprot.org/core/title | "AMP-18 Targets p21 to Maintain Epithelial Homeostasis."xsd:string |
| http://purl.uniprot.org/citations/25919700 | http://purl.uniprot.org/core/volume | "10"xsd:string |
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