| First Author | Peter MR | Year | 2014 |
| Journal | Mediators Inflamm | Volume | 2014 |
| Pages | 767185 | PubMed ID | 25114380 |
| Mgi Jnum | J:345740 | Mgi Id | MGI:6832258 |
| Doi | 10.1155/2014/767185 | Citation | Peter MR, et al. (2014) Impaired resolution of inflammation in the Endoglin heterozygous mouse model of chronic colitis. Mediators Inflamm 2014:767185 |
| abstractText | Endoglin is a coreceptor of the TGF-beta 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-beta1, which was associated with reduced expression of thrombospondin-1, an angiostatic factor known to activate TGF-beta1. We also demonstrate dysregulated expression of BMPER and follistatin, which are extracellular regulators of the TGF-beta 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-beta superfamily mediated resolution of inflammation and fully functional myeloid cells. |
