Journal Article

DKFZ-2017-03848

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Semaphorin-3C signals through Neuropilin-1 and PlexinD1 receptors to inhibit pathological angiogenesis.

Yang, W.-J. (First author)DKFZ* ; Hu, J. (Last author)DKFZ* ; Uemura, A. ; Tetzlaff, F.DKFZ* ; Augustin, H.DKFZ* ; Fischer, A. (Last author)DKFZ*

2015
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.15252/emmm.201404922

Abstract: Retinopathy of prematurity causes visual impairment due to destructive neoangiogenesis after degeneration of the retinal microvasculature. This study was aimed at analyzing whether local delivery of Semaphorin-3C (Sema3C) suppresses pathological retinal angiogenesis. Sema3C exerted potent inhibiting effects in cellular models of angiogenesis. In an endothelial cell xenotransplantation assay, Sema3C acted primarily on immature microvessels by inducing endothelial cell apoptosis. Intravitreal administration of recombinant Sema3C disrupted endothelial tip cell formation and cell-cell contacts, which led to decreased vascular bed expansion and vessel branching in the growing retinal vasculature of newborn mice, while not affecting mature vessels in the adult retina. Sema3C administration strongly inhibited the formation of pathological pre-retinal vascular tufts during oxygen-induced retinopathy. Mechanistically, Sema3C signaled through the receptors Neuropilin-1 and PlexinD1, which were strongly expressed on vascular tufts, induced VE-cadherin internalization, and abrogated vascular endothelial growth factor (VEGF)-induced activation of the kinases AKT, FAK, and p38MAPK. This disrupted endothelial cell junctions, focal adhesions, and cytoskeleton assembly resulted in decreased cell migration and survival. Thus, this study identified Sema3C as a potent and selective inhibitor of pathological retinal angiogenesis.

Keyword(s): Angiogenesis Inhibitors ; Membrane Glycoproteins ; Nerve Tissue Proteins ; Plxnd1 protein, mouse ; Semaphorins ; Neuropilin-1

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Contributing Institute(s):

1. Vaskuläre Signaltransduktion und Krebs (A270)
2. Vaskuläre Onkologie und Metastasierung (A190)

Research Program(s):

1. 321 - Basic Concepts (POF3-321) (POF3-321)

Appears in the scientific report 2015

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Database coverage:
; ; ; BIOSIS Previews ; DOAJ Seal ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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