| Autor: |
Hellmut G. Augustin, Thomas Hielscher, Carolin Mogler, Isidora Paredes, Rosario Yerbes, Aida Freire-Valls, Lena Claesson-Welsh, Abelardo López-Rivas, Xiaohong Wang, Ralf H. Adams, Carmen Ruiz de Almodovar, W. Wei-Lynn Wong, Laura Castro, Thomas Schmidt, Boris Strilic, Peter Heiduschka, Leigh Coultas, Rosa Martín-Pérez, Massimiliano Mazzone, Hermann Josef Gröne, Nathalie Tisch, Silvia La Porta |
| Rok vydání: |
2019 |
| Předmět: |
|
| Popis: |
During developmental angiogenesis blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether and how cell death signaling molecules contribute to blood vessel formation is still not well understood. Caspase-8 (Casp-8), a key protease in the extrinsic cell death-signaling pathway, regulates both cell death via apoptosis and necroptosis. Here we show that expression of Casp-8 in endothelial cells (ECs) is required for proper postnatal angiogenesis. EC specific Casp-8 knockout pups (Casp-8ECko) have reduced retinal angiogenesis, as the loss of Casp-8 reduced EC proliferation, sprouting and migration independent of its cell death function. Instead, the loss of Casp-8 caused hyperactivation of p38 mitogen-activated protein kinase (MAPK) downstream of receptorinteracting serine/threonine-protein kinase 3 (RIPK3) and destabilization of VE-cadherin at EC junctions. In a mouse model of oxygen-induced retinopathy (OIR), resembling retinopathy of prematurity (ROP), loss of Casp-8 in ECs is beneficial, as pathological neovascularization was reduced in Casp-8ECkopups. Taken together, we identify that Casp-8 signals in a cell-death independent manner in ECs during postnatal and pathological blood vessel formation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
