抄録
PURPOSE. Vascular adhesion protein (VAP)-1, a multifunctional molecule with adhesive and enzymatic properties, is expressed at the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity. This study explores a link between increased level of sVAP-1 and oxidative stress in proliferative diabetic retinopathy (PDR) with a focus on mechanistic components to form sVAP-1 by shedding from retinal endothelial cells. METHODS. Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with PDR or non-PDR were measured by ELISA. The mechanism of VAP-1 shedding under diabetic condition, exposure to high glucose and/or inflammatory cytokines, was explored using cultured retinal capillary endothelial cells. RESULTS. Protein level of sVAP-1 was increased and correlated with HEL in the vitreous fluid of patients with PDR. Retinal capillary endothelial cells released sVAP-1 when stimulated with high glucose or inflammatory cytokines, such as TNF-α and IL-1β in vitro. Furthermore, matrix metalloproteinase-2 and -9, type IV collagenases, were the key molecules to mediate the protein cleavage of VAP-1 from retinal capillary endothelial cells. CONCLUSIONS. Our data for the first time provide evidence on the link between sVAP-1 and type IV collagenases in the pathogenesis of PDR.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 4055-4062 |
| ページ数 | 8 |
| ジャーナル | Investigative Ophthalmology and Visual Science |
| 巻 | 53 |
| 発行部数 | 7 |
| DOI | |
| 出版物ステータス | Published - 2012 6 |
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ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
- Medicine(all)
これを引用
Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy. / Murata, Miyuki; Noda, Kousuke; Fukuhara, Junichi; Kanda, Atsuhiro; Kase, Satoru; Saito, Wataru; Ozawa, Yoko; Mochizuki, Satsuki; Kimura, Shioko; Mashima, Yukihiko; Okada, Yasunori; Ishida, Susumu.
：: Investigative Ophthalmology and Visual Science, 巻 53, 番号 7, 06.2012, p. 4055-4062.研究成果: Article
}
TY - JOUR
T1 - Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy
AU - Murata, Miyuki
AU - Noda, Kousuke
AU - Fukuhara, Junichi
AU - Kanda, Atsuhiro
AU - Kase, Satoru
AU - Saito, Wataru
AU - Ozawa, Yoko
AU - Mochizuki, Satsuki
AU - Kimura, Shioko
AU - Mashima, Yukihiko
AU - Okada, Yasunori
AU - Ishida, Susumu
PY - 2012/6
Y1 - 2012/6
N2 - PURPOSE. Vascular adhesion protein (VAP)-1, a multifunctional molecule with adhesive and enzymatic properties, is expressed at the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity. This study explores a link between increased level of sVAP-1 and oxidative stress in proliferative diabetic retinopathy (PDR) with a focus on mechanistic components to form sVAP-1 by shedding from retinal endothelial cells. METHODS. Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with PDR or non-PDR were measured by ELISA. The mechanism of VAP-1 shedding under diabetic condition, exposure to high glucose and/or inflammatory cytokines, was explored using cultured retinal capillary endothelial cells. RESULTS. Protein level of sVAP-1 was increased and correlated with HEL in the vitreous fluid of patients with PDR. Retinal capillary endothelial cells released sVAP-1 when stimulated with high glucose or inflammatory cytokines, such as TNF-α and IL-1β in vitro. Furthermore, matrix metalloproteinase-2 and -9, type IV collagenases, were the key molecules to mediate the protein cleavage of VAP-1 from retinal capillary endothelial cells. CONCLUSIONS. Our data for the first time provide evidence on the link between sVAP-1 and type IV collagenases in the pathogenesis of PDR.
AB - PURPOSE. Vascular adhesion protein (VAP)-1, a multifunctional molecule with adhesive and enzymatic properties, is expressed at the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity. This study explores a link between increased level of sVAP-1 and oxidative stress in proliferative diabetic retinopathy (PDR) with a focus on mechanistic components to form sVAP-1 by shedding from retinal endothelial cells. METHODS. Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with PDR or non-PDR were measured by ELISA. The mechanism of VAP-1 shedding under diabetic condition, exposure to high glucose and/or inflammatory cytokines, was explored using cultured retinal capillary endothelial cells. RESULTS. Protein level of sVAP-1 was increased and correlated with HEL in the vitreous fluid of patients with PDR. Retinal capillary endothelial cells released sVAP-1 when stimulated with high glucose or inflammatory cytokines, such as TNF-α and IL-1β in vitro. Furthermore, matrix metalloproteinase-2 and -9, type IV collagenases, were the key molecules to mediate the protein cleavage of VAP-1 from retinal capillary endothelial cells. CONCLUSIONS. Our data for the first time provide evidence on the link between sVAP-1 and type IV collagenases in the pathogenesis of PDR.
UR - http://www.scopus.com/inward/record.url?scp=84867794144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867794144&partnerID=8YFLogxK
U2 - 10.1167/iovs.12-9857
DO - 10.1167/iovs.12-9857
M3 - Article
C2 - 22618595
AN - SCOPUS:84867794144
VL - 53
SP - 4055
EP - 4062
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 7
ER -