NDLI: Vasculotide, an Angiopoietin-1 mimetic, ameliorates several features of experimental atopic dermatitis-like disease

Content Provider	Springer Nature : BioMed Central
Author	Bourdeau, Annie Van Slyke, Paul Kim, Harold Cruz, Maribelle Smith, Tracy Dumont, Daniel J.
Abstract	Background Earlier studies by our group have demonstrated that a transgenic animal engineered to express Tie2 under the control of the Tie2 promoter produced animals with a scaly skin phenotype that recapitulated many of the hallmarks of atopic dermatitis (AT-Derm). To test the hypothesis that this model of AT-Derm is driven by dysregulated Tie2-signalling, we have bred AT-Derm transgenic (TG) animals with TG-animals engineered to overexpress Angiopoietin-1 or -2, the cognate Tie2 ligands. These two ligands act to antagonize one another in a context-dependent manner. To further evaluate the role of Ang1-driven-Tie2 signalling, we examined the ability of Vasculotide, an Ang1-mimetic, to modulate the AT-Derm phenotype. Results AT-Derm+Ang2 animals exhibited an accentuated phenotype, whereas AT-Derm+Ang1 presented with a markedly reduced skin disease, similarly VT-treated AT-Derm animals present with a clear decrease in the skin phenotype. Moreover, a decrease in several important inflammatory cytokines and a decrease in the number of eosinophils was noted in VT-treated animals. Bone marrow differentiation in the presence of VT produced fewer CFU-G colonies, further supporting a role for Tie2-signalling in eosinophil development. Importantly, we demonstrate activation of Tie2, the VT-target, in lung tissue from naïve animals treated with increasing amounts of VT. Conclusions The AT-Derm phenotype in these animals is driven through dysregulation of Tie2 receptor signalling and is augmented by supplemental Ang2-dependent stimulation. Overexpression of Ang1 or treatment with VT produced a similar amelioration of the phenotype supporting the contention that VT and Ang1 have a similar mechanism of action on the Tie2 receptor and can both counteract the signalling driven by Ang2. Our results also support a possible role for Tie2-signalling in the development of eosinophilic diseases and that activation of Tie2 may directly or indirectly modulate the differentiation of eosinophils, which express Tie2. In summary, these data support the hypothesis that this AT-Derm mouse model is driven by dysregulation of the Tie2 signalling pathway and increased Ang2 levels can aggravate it, whereas it can be reversed by either Ang1-overexpression or VT treatment. Moreover, our data supports the contention that VT acts as an Angiopoietin-1 mimetic and may provide a novel entry point for Tie2-agonist-based therapies for atopic diseases.
Related Links	https://bmcresnotes.biomedcentral.com/counter/pdf/10.1186/s13104-015-1817-1.pdf
Ending Page	7
Page Count	7
Starting Page	1
File Format	HTM / HTML
ISSN	17560500
DOI	10.1186/s13104-015-1817-1
Journal	BMC Research Notes
Issue Number	1
Volume Number	9
Language	English
Publisher	BioMed Central
Publisher Date	2016-05-28
Access Restriction	Open
Subject Keyword	Biomedicine Medicine Public Health Life Sciences Tie2 Atopy Eosinophil Inflammation Angiopoietin Vasculotide Psoriasis Atopic dermatitis Medicine/Public Health
Content Type	Text
Subject	Biochemistry, Genetics and Molecular Biology Medicine
Journal Impact Factor	1.6/2023

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