Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-3-19
pubmed:abstractText
Inflammatory bowel disease (IBD) affects more than 1 million Americans with more than 30,000 new cases diagnosed each year. IBD increases patient morbidity and susceptibility to colorectal cancer, yet its etiology remains unknown. Current models identify two key determinants of IBD pathogenesis: hyperpermeability of the gut epithelial barrier to bacterial products and an abnormal immune response to these products. Two factors seem critical for hyperpermeability: oxidant-induced stress and proinflammatory cytokines (e.g., tumor necrosis factor-alpha). The aim of this study was to investigate the role of oxidant stress-mediated transactivation of the epidermal growth factor receptor (EGFR) in intestinal hyperpermeability. This study used the Caco-2 human colonic epithelial cell in vitro model of intestinal epithelium. Cells were grown on inserts for permeability and signaling studies and glass coverslips for microscopy studies. show that oxidant-induced intestinal hyperpermeability can be blocked by specific inhibitors of the EGFR, tumor necrosis factor convertase (TACE) metalloprotease, transforming growth factor (TGF)-alpha, and mitogen-activated protein kinases, especially extracellular signal-regulated kinase 1/2. We also show that oxidant initiates these signaling events, in part by causing translocation of TACE to cell-cell contact zones. In this study, our data identify a novel mechanism for oxidant-induced intestinal hyperpermeability relevant to IBD. We propose a new intestinal permeability model in which oxidant transactivates EGFR signaling by activation of TACE and cleavage of precursor TGF-alpha. These data could have a significant effect on our view of IBD pathogenesis and provide new therapeutic targets for IBD treatment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/ADAM Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide, http://linkedlifedata.com/resource/pubmed/chemical/Metalloproteases, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Oxidants, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha, http://linkedlifedata.com/resource/pubmed/chemical/tumor necrosis factor-alpha...
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
321
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
84-97
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17220428-ADAM Proteins, pubmed-meshheading:17220428-Blotting, Western, pubmed-meshheading:17220428-Caco-2 Cells, pubmed-meshheading:17220428-Epidermal Growth Factor, pubmed-meshheading:17220428-Humans, pubmed-meshheading:17220428-Hydrogen Peroxide, pubmed-meshheading:17220428-Image Processing, Computer-Assisted, pubmed-meshheading:17220428-Inflammatory Bowel Diseases, pubmed-meshheading:17220428-Intercellular Junctions, pubmed-meshheading:17220428-Intestinal Mucosa, pubmed-meshheading:17220428-Metalloproteases, pubmed-meshheading:17220428-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:17220428-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:17220428-Mitogen-Activated Protein Kinases, pubmed-meshheading:17220428-Oxidants, pubmed-meshheading:17220428-Oxidative Stress, pubmed-meshheading:17220428-Permeability, pubmed-meshheading:17220428-RNA, Neoplasm, pubmed-meshheading:17220428-RNA, Small Interfering, pubmed-meshheading:17220428-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17220428-Signal Transduction, pubmed-meshheading:17220428-Transcriptional Activation, pubmed-meshheading:17220428-Transforming Growth Factor alpha
pubmed:year
2007
pubmed:articleTitle
Regulation of oxidant-induced intestinal permeability by metalloprotease-dependent epidermal growth factor receptor signaling.
pubmed:affiliation
Department of Internal Medicine, Section of Gastroenterology, Rush University Medical Center, 1725 W. Harrison, Suite 206, Chicago, IL 60612, USA. christopher_b_forsyth@rush.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural