[A novel molecular mechanism involving neuropilin-1 for vascular endothelial growth factor-induced retinal angiogenesis].
OBJECTIVE
The Neuropilin (NRP) family is a novel receptor family that has been found to bind to a key molecule in angiogenesis, vascular endothelial growth factor (VEGF). In vascular endothelial cells, NRP-1 functions as an isoform-specific receptor for VEGF165 and has predominant expression compared to NRP-2. Since little is known about its role in pathologic angiogenesis, we studied it in retinal angiogenesis.


RESULTS
In cultured bovine retinal endothelial cells (BREC), VEGF selectively up-regulates NRP-1 expression. This response is mediated by VEGF receptor-2 (VEGFR-2) and transcriptional activation. NRP-1 functional blocking antibody inhibited VEGF-induced mitogenesis of BRECs in vitro. Moreover, inhibition of NRP-1 in a murine model of angioproliferative retinopathy reduced angiogenic response in the retina.


CONCLUSIONS
Our results suggest that NRP-1 plays a critical role in VEGF-induced retinal angiogenesis and thus could be a viable therapeutic target for inhibition of retinal neovascularization.
Oh
Hideyasu
H
Department of Ophthalmology & Visual Sciences, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaramachi, Sakyo-ku, Kyoto 606-8507, Japan.
D000818:Animals; D002417:Cattle; D066298:In Vitro Techniques; D051379:Mice; D039942:Neuropilin-1 / Q000502:physiology*; D015861:Retinal Neovascularization / Q000503:physiopathology*; D042442:Vascular Endothelial Growth Factors / Q000502:physiology*
D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1