Endoglin is a coreceptor of the TGF-βsuperfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated thatEndoglinheterozygous (Eng+/−) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and pathological angiogenesis. We now report that coliticEng+/−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-βsuperfamily that modulate angiogenesis and inflammation. Heightened colonic levels of the neutrophil chemoattractant and proangiogenic factor, CXCL1, were also observed in DSS-treatedEng+/−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 inEng+/−mice undergoing persistent inflammation. Taken together, these findings suggest that endoglin is required for TGF-βsuperfamily mediated resolution of inflammation and fully functional myeloid cells.
Amelioration of Dextran Sulfate Sodium-induced Chronic Colitis by Sulfasalazine Salicylazosulfapyridine via Reducing NF-κB Transcription Factor p65 Recruitment to ICAM-1 Gene Promoters
