title: A zebrafish model of inflammatory lymphangiogenesis.
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 vegfaa, vegfc and vegfd 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.
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Kazuhide S
authors.initials: KS
authors.lastname: Okuda
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: June Pauline
authors.initials: JP
authors.lastname: Misa
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham 27710, USA.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Oehlers
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hall
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Felix
authors.initials: F
authors.lastname: Ellett
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Sultan
authors.initials: S
authors.lastname: Alasmari
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Lieschke
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Crosier
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Crosier
authors.affiliation: Department of Molecular Medicine & Pathology, School of Medical Sciences, University of Auckland, Auckland 1142, New Zealand j.astin@auckland.ac.nz.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Astin
keywords: Inflammation; Inflammatory bowel disease; Lymphatic; Zebrafish