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NADPH Oxidase 4-Derived H 2O 2 Promotes Aberrant Retinal Neovascularization via Activation of VEGF Receptor 2 Pathway in Oxygen-Induced Retinopathy
Joint Authors
Wang, Josh J.
Li, Jingming
Zhang, Sarah X.
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-03-18
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
NADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidase in retinal endothelial cells.
Our previous study suggests that upregulation of Nox4 in retinal endothelial cells contributes to retinal vascular leakage in diabetes.
In the current study, we investigated the role and mechanism of Nox4 in regulation of retinal neovascularization (NV), a hallmark of proliferative diabetic retinopathy (PDR), using a mouse model of oxygen-induced retinopathy (OIR).
Our results confirmed that Nox4 was expressed predominantly in retinal vasculature of mouse retina.
Retinal expression of Nox4 was markedly increased in OIR, in parallel with enhanced phosphorylation of ERK.
In human retinal microvascular endothelial cells (HRECs), overexpression of Nox4 by adenovirus significantly increased extracellular H2O2 generation, resulting in intensified VEGFR2 activation and exacerbated angiogenesis upon VEGF stimulation.
In contrast, silencing Nox4 expression or scavenging H2O2 by polyethylene glycol- (PEG-) conjugated catalase inhibited endothelial migration, tube formation, and VEGF-induced activation of VEGFR2 signaling.
Importantly, knockdown of retinal Nox4 by adenovirus-delivered siRNA significantly reduced ERK activation and attenuated retinal NV formation in OIR.
Taken together, our data indicate that Nox4 promotes retinal NV formation through H2O2/VEGFR2/ERK signaling pathway.
Reducing retinal Nox4 expression may represent a promising therapeutic approach for neovascular retinal diseases such as PDR.
American Psychological Association (APA)
Li, Jingming& Wang, Josh J.& Zhang, Sarah X.. 2015. NADPH Oxidase 4-Derived H 2O 2 Promotes Aberrant Retinal Neovascularization via Activation of VEGF Receptor 2 Pathway in Oxygen-Induced Retinopathy. Journal of Diabetes Research،Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1068041
Modern Language Association (MLA)
Li, Jingming…[et al.]. NADPH Oxidase 4-Derived H 2O 2 Promotes Aberrant Retinal Neovascularization via Activation of VEGF Receptor 2 Pathway in Oxygen-Induced Retinopathy. Journal of Diabetes Research No. 2015 (2015), pp.1-13.
https://search.emarefa.net/detail/BIM-1068041
American Medical Association (AMA)
Li, Jingming& Wang, Josh J.& Zhang, Sarah X.. NADPH Oxidase 4-Derived H 2O 2 Promotes Aberrant Retinal Neovascularization via Activation of VEGF Receptor 2 Pathway in Oxygen-Induced Retinopathy. Journal of Diabetes Research. 2015. Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1068041
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1068041