TY  - JOUR
AU  - Feng, Yuxi
AU  - Gross, Shalini
AU  - Wolf, Nadine M
AU  - Butenschön, Vicki M
AU  - Qiu, Yi
AU  - Devraj, Kavi
AU  - Liebner, Stefan
AU  - Kroll, Jens
AU  - Skolnik, Edward Y
AU  - Hammes, Hans-Peter
AU  - Wieland, Thomas
TI  - Nucleoside diphosphate kinase B regulates angiogenesis through modulation of vascular endothelial growth factor receptor type 2 and endothelial adherens junction proteins.
JO  - Arteriosclerosis, thrombosis, and vascular biology
VL  - 34
IS  - 10
SN  - 1524-4636
CY  - Philadelphia, Pa.
PB  - Lippincott, Williams & Wilkins
M1  - DKFZ-2017-00520
SP  - 2292 - 2300
PY  - 2014
AB  - Nucleoside diphosphate kinase B (NDPKB) participates in the activation of heterotrimeric and monomeric G proteins, which are pivotal mediators in angiogenic signaling. The role of NDPKB in angiogenesis has to date not been defined. Therefore, we analyzed the contribution of NDPKB to angiogenesis and its underlying mechanisms in well-characterized in vivo and in vitro models.Zebrafish embryos were depleted of NDPKB by morpholino-mediated knockdown. These larvae displayed severe malformations specifically in vessels formed by angiogenesis. NDPKB-deficient (NDPKB(-/-)) mice were subjected to oxygen-induced retinopathy. In this model, the number of preretinal neovascularizations in NDPKB(-/-) mice was strongly reduced in comparison with wild-type littermates. In accordance, a delayed blood flow recovery was detected in the NDPKB(-/-) mice after hindlimb ligation. In in vitro studies, a small interfering RNA-mediated knockdown of NDPKB was performed in human umbilical endothelial cells. NDPKB depletion impaired vascular endothelial growth factor (VEGF)-induced sprouting and hampered the VEGF-induced spatial redistributions of the VEGF receptor type 2 and VE-cadherin at the plasma membrane. Concomitantly, NDPKB depletion increased the permeability of the human umbilical endothelial cell monolayer.This is the first report to show that NDPKB is required for VEGF-induced angiogenesis and contributes to the correct localization of VEGF receptor type 2 and VE-cadherin at the endothelial adherens junctions. Therefore, our data identify NDPKB as a novel molecular target to modulate VEGF-dependent angiogenesis.
KW  - Antigens, CD (NLM Chemicals)
KW  - Cadherins (NLM Chemicals)
KW  - NM23 Nucleoside Diphosphate Kinases (NLM Chemicals)
KW  - Zebrafish Proteins (NLM Chemicals)
KW  - cadherin 5 (NLM Chemicals)
KW  - KDR protein, human (NLM Chemicals)
KW  - Vascular Endothelial Growth Factor Receptor-2 (NLM Chemicals)
KW  - NME2 protein, human (NLM Chemicals)
KW  - Nme2 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25147336
DO  - DOI:10.1161/ATVBAHA.114.304239
UR  - https://inrepo02.dkfz.de/record/119929
ER  -