A zebrafish model of inflammatory lymphangiogenesis
Identifieur interne : 007883 ( Ncbi/Checkpoint ); précédent : 007882; suivant : 007884A zebrafish model of inflammatory lymphangiogenesis
Auteurs : Kazuhide S. Okuda [Nouvelle-Zélande] ; June Pauline Misa [Nouvelle-Zélande] ; Stefan H. Oehlers [États-Unis] ; Christopher J. Hall [Nouvelle-Zélande] ; Felix Ellett [Australie] ; Sultan Alasmari [Australie] ; Graham J. Lieschke [Australie] ; Kathryn E. Crosier [Nouvelle-Zélande] ; Philip S. Crosier [Nouvelle-Zélande] ; Jonathan W. Astin [Nouvelle-Zélande]Source :
- Biology Open [ 2046-6390 ] ; 2015.
Abstract
Inflammatory bowel disease (IBD) is a disabling chronic inflammatory disease of the gastrointestinal tract. IBD patients have increased intestinal lymphatic vessel density and recent studies have shown that this may contribute to the resolution of IBD. However, the molecular mechanisms involved in IBD-associated lymphangiogenesis are still unclear. In this study, we established a novel inflammatory lymphangiogenesis model in zebrafish larvae involving colitogenic challenge stimulated by exposure to 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sodium sulphate (DSS). Treatment with either TNBS or DSS resulted in vascular endothelial growth factor receptor (Vegfr)-dependent lymphangiogenesis in the zebrafish intestine. Reduction of intestinal inflammation by the administration of the IBD therapeutic, 5-aminosalicylic acid, reduced intestinal lymphatic expansion. Zebrafish macrophages express vascular growth factors
Url:
DOI: 10.1242/bio.013540
PubMed: 26369931
PubMed Central: 4610225
Affiliations:
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<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>Inflammatory bowel disease (IBD) is a disabling chronic inflammatory disease of the gastrointestinal tract. IBD patients have increased intestinal lymphatic vessel density and recent studies have shown that this may contribute to the resolution of IBD. However, the molecular mechanisms involved in IBD-associated lymphangiogenesis are still unclear. In this study, we established a novel inflammatory lymphangiogenesis model in zebrafish larvae involving colitogenic challenge stimulated by exposure to 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sodium sulphate (DSS). Treatment with either TNBS or DSS resulted in vascular endothelial growth factor receptor (Vegfr)-dependent lymphangiogenesis in the zebrafish intestine. Reduction of intestinal inflammation by the administration of the IBD therapeutic, 5-aminosalicylic acid, reduced intestinal lymphatic expansion. Zebrafish macrophages express vascular growth factors <italic>vegfaa</italic>
, <italic>vegfc</italic>
and <italic>vegfd</italic>
and chemical ablation of these cells inhibits intestinal lymphatic expansion, suggesting that the recruitment of macrophages to the intestine upon colitogenic challenge is required for intestinal inflammatory lymphangiogenesis. Importantly, this study highlights the potential of zebrafish as an inflammatory lymphangiogenesis model that can be used to investigate the role and mechanism of lymphangiogenesis in inflammatory diseases such as IBD.</p>
</div>
</front>
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