RT Journal Article
T1 Caspase-8 modulates physiological and pathological angiogenesis during retina development.
A1 Tisch, Nathalie
A1 Freire-Valls, Aida
A1 Yerbes, Rosario
A1 Paredes, Isidora
A1 La Porta, Silvia
A1 Wang, Xiaohong
A1 Martín-Pérez, Rosa
A1 Castro, Laura
A1 Wong, Wendy Wei-Lynn
A1 Coultas, Leigh
A1 Strilic, Boris
A1 Gröne, Hermann-Josef
A1 Hielscher, Thomas
A1 Mogler, Carolin
A1 Adams, Ralf H
A1 Heiduschka, Peter
A1 Claesson-Welsh, Lena
A1 Mazzone, Massimiliano
A1 López-Rivas, Abelardo
A1 Schmidt, Thomas
A1 Augustin, Hellmut G
A1 Ruiz de Almodovar, Carmen
K1 Angiogenesis
K1 Apoptosis pathways
K1 Caspases and caspase substrates
K1 Retinopathy
AB During developmental angiogenesis, blood vessels grow and remodel to ultimately build a hierarchical vascular network. Whether, 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 cell death via both apoptosis and necroptosis. Here, we show that expression of Casp-8 in endothelial cells (ECs) is required for proper postnatal retina angiogenesis. EC-specific Casp-8-KO pups (Casp-8ECKO) showed reduced retina angiogenesis, as the loss of Casp-8 reduced EC proliferation, sprouting, and migration independently of its cell death function. Instead, the loss of Casp-8 caused hyperactivation of p38 MAPK downstream of receptor-interacting serine/threonine protein kinase 3 (RIPK3) and destabilization of vascular endothelial cadherin (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 was beneficial, as pathological neovascularization was reduced in Casp-8ECKO pups. Taking these data together, we show that Casp-8 acts in a cell death-independent manner in ECs to regulate the formation of the retina vasculature and that Casp-8 in ECs is mechanistically involved in the pathophysiology of ROP.
YR 2019
FD 2019
LK http://hdl.handle.net/10668/14448
UL http://hdl.handle.net/10668/14448
LA en
DS RISalud
RD Apr 6, 2025