title: Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis.
abstract: Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD.
authors.affiliation: Institute of Digestive Disease, Department of Gastroenterology, Tongji Hospital affiliated to Tongji University, Shanghai, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Wang
authors.affiliation: Institute of Digestive Disease, Department of Gastroenterology, Tongji Hospital affiliated to Tongji University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Digestive Disease, Department of Gastroenterology, Tongji Hospital affiliated to Tongji University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.affiliation: Institute of Digestive Disease, Department of Gastroenterology, Tongji Hospital affiliated to Tongji University, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Qiao
mesh_terms: D000208:Acute Disease; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003092:Colitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology; D042583:Lymphangiogenesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011995:Recombination, Genetic / Q000502:physiology; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism* / Q000502:physiology
chemical_list: D042582:Vascular Endothelial Growth Factor C