Files
Document type
ArticleVersion
Published versionPublication date
Publication license
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/155801
VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
Journal Title
Director/Tutor
Journal ISSN
Volume Title
Related resource
Abstract
During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch inhibition exacerbates podosome formation and collagen-IV loss. We propose that the localized proteolytic action of podosomes on basement membrane collagen-IV facilitates endothelial cell sprouting and anastomosis within the developing vasculature. The identification of podosomes as key components of the sprouting machinery provides another opportunity to target angiogenesis therapeutically.
Subject (English)
Citation
Citation
SPUUL, Pirjo, et al. VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis. Cell Reports. 2016. Vol. 17, num. 2, pags. 484-500. ISSN 2211-1247. [consulted: 8 of August of 2026]. Available at: https://hdl.handle.net/2445/155801