2026-04-13T01:05:07Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1558012025-12-05T09:23:02Zcom_2072_1057col_2072_478799col_2072_478917

00925njm 22002777a 4500 dc Spuul, Pirjo author Daubon, Thomas author Pitter, Bettina author Alonso, Florian author Fremaux, Isabelle author Kramer, Ijsbrand author Montañez, Eloi author Génot, Elisabeth author 2020-04-17T11:44:20Z 2020-04-17T11:44:20Z 2016-10-04 2020-04-17T11:44:21Z 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. Col·lagen Genètica Metabolisme Factor de creixement de l'endoteli vascular Collagen Genetics Metabolism Vascular endothelial growth factors VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis