| Matriptase protects against experimental colitis and promotes intestinal barrier recovery. | |
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MedLine Citation:
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PMID: 22081509 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Matriptase is a membrane-anchored serine protease encoded by suppression of tumorigenicity-14 (ST14) that is required for epithelial barrier homeostasis. However, its functional role in inflammatory bowel disease (IBD) is unexplored. METHODS: Matriptase expression in control, Crohn's disease, and ulcerative colitis tissue specimens was studied by quantitative polymerase chain reaction (qPCR) and immunostaining. Matriptase function was investigated by subjecting St14 hypomorphic and control littermates to dextran sodium sulfate (DSS)-induced colitis and by siRNA silencing in cultured monolayers. Mice were analyzed for clinical, histological, molecular, and cellular effects. RESULTS: Matriptase protein and ST14 mRNA levels are significantly downregulated in inflamed colonic tissues from Crohn's disease and ulcerative colitis patients. Matriptase-deficient St14 hypomorphic mice administered DSS for 7 days followed by water without DSS for 3 days develop a severe colitis, with only 30% of the St14 hypomorphic mice surviving to day 14, compared with 100% of control littermates. Persistent colitis in surviving St14 hypomorphic mice was associated with sustained cytokine production, an inability to recover barrier integrity, and enhanced claudin-2 expression. Cytokines implicated in barrier disruption during IBD suppress matriptase expression in T84 epithelial monolayers and restoration of matriptase improves barrier integrity in the cytokine-perturbed monolayers. CONCLUSIONS: These data demonstrate a critical role for matriptase in restoring barrier function to injured intestinal mucosa during colitis, which is suppressed by excessive activation of the immune system. Strategies to enhance matriptase-mediated barrier recovery could be important for intervening in the cycle of inflammation associated with IBD. |
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Authors:
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Sarah Netzel-Arnett; Marguerite S Buzza; Terez Shea-Donohue; Antoine Désilets; Richard Leduc; Alessio Fasano; Thomas H Bugge; Toni M Antalis |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2011-11-13 |
Journal Detail:
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Title: Inflammatory bowel diseases Volume: 18 ISSN: 1536-4844 ISO Abbreviation: Inflamm. Bowel Dis. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-12 Completed Date: 2012-10-18 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 9508162 Medline TA: Inflamm Bowel Dis Country: United States |
Other Details:
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Languages: eng Pagination: 1303-14 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Crohn's & Colitis Foundation of America, Inc. |
Affiliation:
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Center for Vascular and Inflammatory Diseases and Department of Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Québec, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Colitis / chemically induced, pathology, prevention & control* Colitis, Ulcerative / genetics, metabolism*, pathology Colon / enzymology, pathology Crohn Disease / genetics, metabolism*, pathology Dextran Sulfate / toxicity Disease Models, Animal Electric Impedance Female Humans Immunoenzyme Techniques Intestines / enzymology*, injuries Male Mice Mice, Inbred C57BL RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Serine Endopeptidases / genetics, metabolism*, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AI/DK49316/AI/NIAID NIH HHS; CA098369/CA/NCI NIH HHS; DK081376/DK/NIDDK NIH HHS; DK48373/DK/NIDDK NIH HHS; HL07698/HL/NHLBI NIH HHS; HL084387/HL/NHLBI NIH HHS; R01 AI049316-10/AI/NIAID NIH HHS; R01 CA098369-05/CA/NCI NIH HHS; R01 DK048373-07/DK/NIDDK NIH HHS; R01 DK048373-07S1/DK/NIDDK NIH HHS; R01 DK048373-07S2/DK/NIDDK NIH HHS; R01 DK081376-01A1/DK/NIDDK NIH HHS; R01 DK081376-02/DK/NIDDK NIH HHS; R01 HL084387-04/HL/NHLBI NIH HHS; T32 HL007698-20/HL/NHLBI NIH HHS; //Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 9042-14-2/Dextran Sulfate; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/St14 protein, mouse; EC 3.4.21.109/ST14 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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