Affiliation:
1. Wihuri Research Institute, Biomedicum Helsinki, Helsinki, Finland
2. Translational Cancer Medicine Research Program, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
3. Individualized Drug Therapy Research Program, Faculty of Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
4. Department of Anatomy, Keio University School of Medicine, Tokyo, Japan
Abstract
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are quintessential for the development and maintenance of blood and lymphatic vessels. However, genetic interactions between the VEGFRs are poorly understood. VEGFR2 is the dominant receptor that is required for the growth and survival of the endothelium, whereas deletion of VEGFR1 or VEGFR3 was reported to induce vasculature overgrowth. Here we show that vascular regression induced by VEGFR2 deletion in postnatal and adult mice is aggravated by additional deletion of VEGFR1 or VEGFR3 in the intestine, kidney, and pancreas, but not in the liver or kidney glomeruli. In the adult mice, hepatic and intestinal vessels regressed within a few days after gene deletion, whereas vessels in skin and retina remained stable for at least four weeks. Our results show changes in endothelial transcriptomes and organ-specific vessel maintenance mechanisms that are dependent on VEGFR signaling pathways and reveal previously unknown functions of VEGFR1 and VEGFR3 in endothelial cells.
Funder
Jenny and Antti Wihuri Foundation
Academy of Finland
Finnish Brain Foundation
European Research Council
European Union’s Horizon 2020 research and innovation program
Novo Nordisk Foundation
Sigrid Jusélius Foundation
Cancer Foundation Finland
Orion Research Foundation
Finnish Foundation for Cardiovascular Research
University of Helsinki
Mary and Georg C. Ehrnrooth Foundation
Swiss National Science Foundation
Maud Kuistila Memorial Foundation
Instrumentarium Foundation
Onni and Hilja Tuovinen Foundation
Emil Aaltonen Foundation
Waldemar von Frenckell Foundation
Ida Montini Foundation
Biomedicum Helsinki Foundation
K. Albin Johansson Foundation
Nylands Nation
Swedish Student Foundation
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
22 articles.
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