Proteolytic cleavage of vascular adhesion protein-1 induced by vascular endothelial growth factor in retinal capillary endothelial cells

Yoshida, Shiho; Murata, Miyuki; Noda, Kousuke; Matsuda, Takashi; Saito, Michiyuki; Saito, Wataru; Kanda, Atsuhiro; Ishida, Susumu

Proteolytic cleavage of vascular adhesion protein-1 induced by vascular endothelial growth factor in retinal capillary endothelial cells

Yoshida, Shiho; Murata, Miyuki; Noda, Kousuke et al.

Japanese Journal of Ophthalmology, 2018, 62(2), 256-264

Permalink : https://hdl.handle.net/2115/72735

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アクセス権	open access
URI	https://hdl.handle.net/2115/72735
タイトル	Proteolytic cleavage of vascular adhesion protein-1 induced by vascular endothelial growth factor in retinal capillary endothelial cells
その他のタイトル	VEGF induces the cleavage of VAP-1
著者	Yoshida, Shiho ; Murata, Miyuki ; Noda, Kousuke ; Matsuda, Takashi ; Saito, Michiyuki ; Saito, Wataru ; Kanda, Atsuhiro ; Ishida, Susumu
著者名 Yoshida, Shiho
著者名 Murata, Miyuki
e-Rad_Researcher 90296666 著者名 Noda, Kousuke
著者名 Matsuda, Takashi
著者名 Saito, Michiyuki
e-Rad_Researcher 00339160 著者名 Saito, Wataru
e-Rad_Researcher 80342707 著者名 Kanda, Atsuhiro
e-Rad_Researcher 10245558 著者名 Ishida, Susumu
言語	英語
キーワード	vascular endothelial growth factor (VEGF)
	vascular adhesion protein-1 (VAP-1)
	semicarbazide-sensitive amine oxidase (SSAO)
	matrix metalloproteinases (MMPs)
発行日	2018-03
出版者	Springer
収録物名	Japanese Journal of Ophthalmology
巻(号)	62(2)
ページ	256-264
抄録	Purpose: To investigate the mechanism of soluble vascular adhesion protein-1 (sVAP-1) accumulation induced by vascular endothelial growth factor (VEGF) in the vitreous of patients with diabetic retinopathy (DR). Study design: Experimental. Methods: Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with proliferative diabetic retinopathy (PDR) with or without intravitreal bevacizumab (IVB) injection were determined by ELISA. The effect of VEGF on both mRNA expression of Vap-1 and secretion of sVAP-1 in rat retinal capillary endothelial cells (TR-iBRB2) was analyzed by real-time PCR and western blotting, respectively. In addition, the impact of VEGF on production and activation ratios of matrix metalloproteinase (MMP)-2 and MMP-9 was examined by gelatin zymography. Hydrogen peroxide production and reactive oxygen species (ROS) levels were assessed in the supernatants of TR-iBRB2 cells treated with VEGF. Results: IVB injection decreased vitreous levels of sVAP-1 and HEL in patients with PDR. VEGF stimulation released sVAP-1 protein from TR-iBRB2 cells as a consequence of membrane-anchored VAP-1 shedding by MMP-2 and MMP-9. In addition, VEGF increased hydrogen peroxide generation and ROS augmentation through spermine oxidation by sVAP-1 as semicarbazide-sensitive amine oxidase (SSAO) in the supernatant of cultured endothelial cells. Conclusions: The current data demonstrate that proangiogenic factor VEGF induces sVAP-1 release from retinal capillary endothelial cells and facilitates hydrogen peroxide generation via enzymatic property of sVAP-1, followed by the increase of oxidative stress, one of the crucial factors in the pathogenesis of DR.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	This is a post-peer-review, pre-copyedit version of an article published in Japanese Journal of Ophthalmology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10384-017-0555-4
PISSN	0021-5155
EISSN	1613-2246
関連情報	PMID 29392528
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1007/s10384-017-0555-4