Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation

Proceedings of the National Academy of Sciences of the United States of America

Volumn 108, Issue 49, 2011, Pages 19830-19835

  Vetrano, Stefania ^a   Ploplis, Victoria A ^b   Sala, Emanuela ^a   Sandoval Cooper, Mayra ^b   Donahue, Deborah L ^b   Correale, Carmen ^a   Arena, Vincenzo ^c   Spinelli, Antonino ^a   Repici, Alessandro ^a   Malesci, Alberto ^a   Castellino, Francis J ^b   Danese, Silvio ^a  

^a HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^b UNIVERSITY OF NOTRE DAME   (United States)

^c CATHOLIC UNIVERSITY   (Italy)

Author keywords

DSS induced colitis; Intestinal barrier integrity; Intestinal permeability and tight junction proteins

Indexed keywords

CLAUDIN 3; JUNCTIONAL ADHESION MOLECULE A; PROTEIN C; PROTEIN ZO1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; COLITIS; CONTROLLED STUDY; DISEASE SEVERITY; DOWN REGULATION; HUMAN; HUMAN CELL; IN VITRO STUDY; INTESTINE EPITHELIUM CELL; INTESTINE MUCOSA PERMEABILITY; MOUSE; NONHUMAN; PERMEABILITY BARRIER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN STRUCTURE;

ANIMALS; ANTICOAGULANTS; ANTIGENS, CD; CACO-2 CELLS; CELLS, CULTURED; COLITIS; EPITHELIAL CELLS; GENE EXPRESSION; HUMANS; IMMUNOHISTOCHEMISTRY; INFLAMMATORY BOWEL DISEASES; INTERLEUKIN-6; INTERLEUKIN-8; INTESTINAL MUCOSA; INTESTINES; MALE; MEMBRANE PROTEINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; PHOSPHOPROTEINS; PROTEIN C; RECEPTORS, CELL SURFACE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TIGHT JUNCTIONS;

EID: 83755195016     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1107140108     Document Type: Article

References (27)

1. Esmon CT (2003) Inflammation and thrombosis. J Thromb Haemost 1:1343-1348.
2. Esmon CT (2004) Interactions between the innate immune and blood coagulation systems. Trends Immunol 25:536-542.
3. Danese S, Vetrano S, Zhang L, Poplis VA, Castellino FJ (2010) The protein C pathway in tissue inflammation and injury: Pathogenic role and therapeutic implications. Blood 115:1121-1130.
4. Esmon CT, et al. (1999) Inflammation, sepsis, and coagulation. Haematologica 84:254-259. (Pubitemid 29476931)
5. Lust M, Vulcano M, Danese S (2008) The protein C pathway in inflammatory bowel disease: The missing link between inflammation and coagulation. Trends Mol Med 14:237-244.
6. Danese S (2008) Nonimmune cells in IBD pathogenesis: From victim to villain. Trends Immunol 29:555-564.
7. Danese S, et al. (2003) Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients. Gastroenterology 124:1249-1264. (Pubitemid 36531801)
8. Danese S, et al. (2007) Inflammation and coagulation in inflammatory bowel disease: The clot thickens. Am J Gastroenterol 102:174-186. (Pubitemid 46072059)
9. Danese S, et al. (2006) Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 130:2060-2073. (Pubitemid 43816964)
10. Scaldaferri F, et al. (2007) Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease. J Clin Invest 117:1951-1960. (Pubitemid 47036329)
11. Vetrano S, et al. (2008) Unique role of junctional adhesion molecule-a in maintaining mucosal homeostasis in inflammatory bowel disease. Gastroenterology 135:173-184. (Pubitemid 351899025)
12. Scaldaferri F, et al. (2009) VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology 136:585-595.
13. Lay AJ, Liang Z, Rosen ED, Castellino FJ (2005) Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities. J Clin Invest 115:1552-1561. (Pubitemid 40814663)
14. Lay AJ, Donahue D, Tsai MJ, Castellino FJ (2007) Acute inflammation is exacerbated in mice genetically predisposed to a severe protein C deficiency. Blood 109:1984-1991. (Pubitemid 46348196)
15. Turner JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9:799-809.
16. Rutgeerts P, Vermeire S, Van Assche G (2007) Mucosal healing in inflammatory bowel disease: Impossible ideal or therapeutic target? Gut 56:453-455. (Pubitemid 46580492)
17. Esmon CT (2001) Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflammation. Crit Care Med 29:S48-S51.
18. Mosnier LO, Zlokovic BV, Griffin JH (2006) The cytoprotective protein C pathway. Blood 109:3161-3172. (Pubitemid 46572500)
19. Groschwitz KR, et al. (2009) Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism. Proc Natl Acad Sci USA 106:22381-22386.
20. Ishii H, Majerus PW (1985) Thrombomodulin is present in human plasma and urine. J Clin Invest 76:2178-2181. (Pubitemid 16155511)
21. Vetrano S, Danese S (2009) The role of JAM-A in inflammatory bowel disease: Unrevealing the ties that bind. Ann N Y Acad Sci 1165:308-313.
22. Young N, Van Brocklyn JR (2006) Signal transduction of sphingosine-1-phosphate G protein-coupled receptors. ScientificWorldJournal 6:946-966. (Pubitemid 44252720)
23. Rosen H, Sanna MG, Cahalan SM, Gonzalez-Cabrera PJ (2007) Tipping the gatekeeper: S1P regulation of endothelial barrier function. Trends Immunol 28:102-107. (Pubitemid 46283694)
24. Greenspon J, et al. (2011) Sphingosine-1-phosphate regulates the expression of adherens junction protein E-cadherin and enhances intestinal epithelial cell barrier function. Dig Dis Sci 56:1342-1353.
25. Mullershausen F, et al. (2009) Persistent signaling induced by FTY720-phosphate is mediated by internalized S1P1 receptors. Nat Chem Biol 5:428-434.
26. Xue M, Thompson P, Kelso I, Jackson C (2004) Activated protein C stimulates proliferation, migration and wound closure, inhibits apoptosis and upregulates MMP-2 activity in cultured human keratinocytes. Exp Cell Res 299:119-127. (Pubitemid 39078387)
27. Whitmont K, et al. (2008) Treatment of chronic leg ulcers with topical activated protein C. Arch Dermatol 144:1479-1483.