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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Arena, Vincenzo Danese, Silvio Correale, Carmen Sala, Emanuela Spinelli, Antonino Vetrano, Stefania Donahue, Deborah L. Castellino, Francis J. Ploplis, Victoria A. Sandoval-cooper, Mayra Malesci, Alberto Repici, Alessandro |
| Description | Author Affiliation: Vetrano S ( IBD Unit, Division of Gastroenterology, Istituto Clinico Humanitas IRCCS, Rozzano 20089 Milan, Italy.); |
| Abstract | The protein C (PC) pathway is a well-characterized coagulation system. Endothelial PC receptors and thrombomodulin mediate the conversion of PC to its activated form, a potent anticoagulant and anti-inflammatory molecule. Here we show that the PC pathway is expressed on intestinal epithelial cells. The epithelial expression of PC and endothelial PC receptor is down-regulated In patients with inflammatory bowel disease. PC(-/-)/PC(Tg) mice, expressing only 3% of WT PC, developed spontaneous intestinal inflammation and were prone to severe experimental colitis. These mice also demonstrated spontaneous elevated production of inflammatory cytokines and increased intestinal permeability. Structural analysis of epithelial tight junction molecules revealed that lack of PC leads to decreased JAM-A and claudin-3 expression and an altered pattern of ZO-1 expression. In vitro, treatment of epithelial cells with activated PC led to protection of tight junction disruption induced by TNF- , and in vivo, topical treatment with activated PC led to mucosal healing and amelioration of colitis. Taken together, these findings demonstrate that the PC pathway is a unique system involved in controlling intestinal homeostasis and inflammation by regulating epithelial barrier function. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 49 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Colitis Genetics Epithelial Cells Metabolism Inflammatory Bowel Diseases Protein C Animals Anticoagulants Pharmacology Antigens, CD Caco-2 Cells Cells, Cultured Drug Effects Pathology Gene Expression Immunohistochemistry Interleukin-6 Interleukin-8 Intestinal Mucosa Intestines Membrane Proteins Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Phosphoproteins Physiology Receptors, Cell Surface Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Tight Junctions Zonula Occludens-1 Protein Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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