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Mediators of Inflammation
Volume 2014 (2014), Article ID 767185, 13 pages
Research Article

Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis

1Molecular Structure and Function Program, The Hospital for Sick Children, Toronto, ON, Canada M5G 0A4
2Department of Immunology, University of Toronto, Toronto, ON, Canada M5S 1A8
3Keenan Research Centre in Li Ka Shing Knowledge Institute, St. Michael’s Hospital, 209 Victoria Street, Toronto, ON, Canada M5B 1T8
4Program in Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, ON, Canada M5G 0A4
5Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 1A8
6Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada M5G 1X8
7Department of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada M5G 1G6
8Institute of Medical Science, University of Toronto, Toronto, ON, Canada M5S 1A8

Received 14 March 2014; Revised 22 May 2014; Accepted 23 May 2014; Published 10 July 2014

Academic Editor: Jean-Marie Reimund

Copyright © 2014 Madonna R. Peter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Endoglin is a coreceptor of the TGF-β superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng+/−) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and pathological angiogenesis. We now report that colitic Eng+/− mice have low colonic levels of active TGF-β1, which was associated with reduced expression of thrombospondin-1, an angiostatic factor known to activate TGF-β1. We also demonstrate dysregulated expression of BMPER and follistatin, which are extracellular regulators of the TGF-β superfamily that modulate angiogenesis and inflammation. Heightened colonic levels of the neutrophil chemoattractant and proangiogenic factor, CXCL1, were also observed in DSS-treated Eng+/− mice. Interestingly, despite increased macrophage and neutrophil infiltration, a gut-specific reduction in expression of the key phagocytic respiratory burst enzymes, NADPH oxidase 2 (Nox-2) and myeloperoxidase, was seen in Eng+/− mice undergoing persistent inflammation. Taken together, these findings suggest that endoglin is required for TGF-β superfamily mediated resolution of inflammation and fully functional myeloid cells.