Interplay of vascular endothelial growth factor receptors in organ-specific vessel maintenance
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...
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| Veröffentlicht in: | The Journal of experimental medicine 2022-03, Vol.219 (3) |
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| creator | Karaman, Sinem Paavonsalo, Satu Heinolainen, Krista Lackman, Madeleine H Ranta, Amanda Hemanthakumar, Karthik A Kubota, Yoshiaki Alitalo, Kari |
| description | 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. |
| doi_str_mv | 10.1084/jem.20210565 |
| format | Article |
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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. 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| subjects | Age Factors Animals Apoptosis Blood Vessels - physiology Cardiovascular Biology Endothelial Cells - metabolism Endothelium - metabolism Gene Deletion Gene Expression Regulation Gene Knockdown Techniques Mice Mice, Knockout Microvascular Density - genetics Multigene Family Neovascularization, Physiologic - genetics Organ Specificity - genetics Phenotype Protein Binding Receptors, Vascular Endothelial Growth Factor - genetics Receptors, Vascular Endothelial Growth Factor - metabolism Signal Transduction Vascular Endothelial Growth Factors - genetics Vascular Endothelial Growth Factors - metabolism |
| title | Interplay of vascular endothelial growth factor receptors in organ-specific vessel maintenance |
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