학술논문

Pericytes regulate VEGF-induced endothelial sprouting through VEGFR1.
Document Type
article
Source
Nature communications. 8(1)
Subject
Eye
Pericytes
Capillaries
Retina
Cell Line
Endothelial Cells
Animals
Mice
Inbred C57BL
Mice
Knockout
Humans
Mice
Diphtheria Toxin
Receptor
Platelet-Derived Growth Factor beta
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor A
Signal Transduction
Neovascularization
Physiologic
Human Umbilical Vein Endothelial Cells
Heparin-binding EGF-like Growth Factor
Eye Disease and Disorders of Vision
Diabetes
1.1 Normal biological development and functioning
2.1 Biological and endogenous factors
Cardiovascular
Inbred C57BL
Knockout
Receptor
Platelet-Derived Growth Factor beta
Neovascularization
Physiologic
MD Multidisciplinary
Language
Abstract
Pericytes adhere to the abluminal surface of endothelial tubules and are required for the formation of stable vascular networks. Defective endothelial cell-pericyte interactions are frequently observed in diseases characterized by compromised vascular integrity such as diabetic retinopathy. Many functional properties of pericytes and their exact role in the regulation of angiogenic blood vessel growth remain elusive. Here we show that pericytes promote endothelial sprouting in the postnatal retinal vasculature. Using genetic and pharmacological approaches, we show that the expression of vascular endothelial growth factor receptor 1 (VEGFR1) by pericytes spatially restricts VEGF signalling. Angiogenic defects caused by pericyte depletion are phenocopied by intraocular injection of VEGF-A or pericyte-specific inactivation of the murine gene encoding VEGFR1. Our findings establish that pericytes promote endothelial sprouting, which results in the loss of side branches and the enlargement of vessels when pericyte function is impaired or lost.