Journal Article

DKFZ-2019-02294

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Caspase-8 modulates physiological and pathological angiogenesis during retina development.

Tisch, N. ; Freire-Valls, A. ; Yerbes, R. ; Paredes, I. ; La Porta, S.DKFZ* ; Wang, X. ; Martín-Pérez, R. ; Castro, L. ; Wong, W. W. ; Coultas, L. ; Strilic, B. ; Gröne, H.-J.DKFZ* ; Hielscher, T.DKFZ* ; Mogler, C. ; Adams, R. ; Heiduschka, P. ; Claesson-Welsh, L. ; Mazzone, M. ; López-Rivas, A. ; Schmidt, T. ; Augustin, H. G.DKFZ* ; Ruiz de Almodovar, C.

2019
ASCJ Ann Arbor, Mich.

This record in other databases:  

Please use a persistent id in citations: doi:10.1172/JCI122767

Abstract: 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) was required for proper postnatal retina angiogenesis. EC specific Casp-8 knockout pups (Casp-8ECko) showed reduced retina 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 receptor-interacting 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 was beneficial, as pathological neovascularization was reduced in Casp-8ECko pups. Taken together, we describe 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.

Note: 2019 Dec 2;129(12):5092-5107

---

Contributing Institute(s):

1. Vaskuläre Onkologie und Metastasierung (A190)
2. Zelluläre und Molekulare Pathologie (G130)
3. Biostatistik (C060)

Research Program(s):

1. 319H - Addenda (POF3-319H) (POF3-319H)

Appears in the scientific report 2019

---

Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

---