Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model

Retinopathy of Prematurity (ROP), a type of retinal neovascularization in premature infants, has become a serious problem that drastically affects the quality of life of premature infants. ROP is associated with angiogenesis and neovascularization. Here, we aimed to explain the function and latent r...

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Autores principales:	Jing Zhang, Qi Xiong, Lin Yang, Yanni Xue, Min Ke, Zhi Li
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	cyp2j2 retinal vascular endothelial cells notch pathway hypoxia-induced retinopathy Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/5e5de2c265c24d939303795672c69e06
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spelling	oai:doaj.org-article:5e5de2c265c24d939303795672c69e062021-12-01T14:41:00ZCytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model2165-59792165-598710.1080/21655979.2021.1994722https://doaj.org/article/5e5de2c265c24d939303795672c69e062021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1994722https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Retinopathy of Prematurity (ROP), a type of retinal neovascularization in premature infants, has become a serious problem that drastically affects the quality of life of premature infants. ROP is associated with angiogenesis and neovascularization. Here, we aimed to explain the function and latent roles of Cytochrome P450 2J2 (CYP2J2) in hypoxia-induced retinopathy in retinal vascular endothelial cells (HRVECs). HRVECs were stimulated with hypoxia for 24 h to establish an in vitro retinopathy model. Cell viability and migration were evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Protein and gene expression was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis. We observed that pcDNA3.1(+)-CYP2J2 promoted CYP2J2 and Jagged1 expression, while Dll4 was down-regulated in hypoxia-stimulated HRVECs. Additionally, pcDNA3.1(+)-CYP2J2 inhibited HRVEC viability, reduced PCNA expression, and inhibited the migration of HRVECs. Further, the Notch pathway was inhibited in the Hypoxia+pcDNA3.1(+)-CYP2J2 group. Opposite results were observed upon Terfenadone treatment in hypoxia induced HRVECs. Finally, our findings further verified that DAPT promotes the effects of CYP2J2 on cell viability, migration, and Notch signaling in hypoxia-induced HRVECs, while EDTA reversed the inhibitory effects of CYP2J2 on hypoxia-induced HRVECs. In conclusions, CYP2J2 was found to inhibit the viability and angiogenesis of HRVECs by inhibiting Notch signaling in a hypoxia-induced retinopathy model.Jing ZhangQi XiongLin YangYanni XueMin KeZhi LiTaylor & Francis Grouparticlecyp2j2retinal vascular endothelial cellsnotch pathwayhypoxia-induced retinopathyBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 10878-10890 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cyp2j2 retinal vascular endothelial cells notch pathway hypoxia-induced retinopathy Biotechnology TP248.13-248.65
spellingShingle	cyp2j2 retinal vascular endothelial cells notch pathway hypoxia-induced retinopathy Biotechnology TP248.13-248.65 Jing Zhang Qi Xiong Lin Yang Yanni Xue Min Ke Zhi Li Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model
description	Retinopathy of Prematurity (ROP), a type of retinal neovascularization in premature infants, has become a serious problem that drastically affects the quality of life of premature infants. ROP is associated with angiogenesis and neovascularization. Here, we aimed to explain the function and latent roles of Cytochrome P450 2J2 (CYP2J2) in hypoxia-induced retinopathy in retinal vascular endothelial cells (HRVECs). HRVECs were stimulated with hypoxia for 24 h to establish an in vitro retinopathy model. Cell viability and migration were evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Transwell assays, respectively. Protein and gene expression was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis. We observed that pcDNA3.1(+)-CYP2J2 promoted CYP2J2 and Jagged1 expression, while Dll4 was down-regulated in hypoxia-stimulated HRVECs. Additionally, pcDNA3.1(+)-CYP2J2 inhibited HRVEC viability, reduced PCNA expression, and inhibited the migration of HRVECs. Further, the Notch pathway was inhibited in the Hypoxia+pcDNA3.1(+)-CYP2J2 group. Opposite results were observed upon Terfenadone treatment in hypoxia induced HRVECs. Finally, our findings further verified that DAPT promotes the effects of CYP2J2 on cell viability, migration, and Notch signaling in hypoxia-induced HRVECs, while EDTA reversed the inhibitory effects of CYP2J2 on hypoxia-induced HRVECs. In conclusions, CYP2J2 was found to inhibit the viability and angiogenesis of HRVECs by inhibiting Notch signaling in a hypoxia-induced retinopathy model.
format	article
author	Jing Zhang Qi Xiong Lin Yang Yanni Xue Min Ke Zhi Li
author_facet	Jing Zhang Qi Xiong Lin Yang Yanni Xue Min Ke Zhi Li
author_sort	Jing Zhang
title	Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model
title_short	Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model
title_full	Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model
title_fullStr	Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model
title_full_unstemmed	Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model
title_sort	cytochrome p450 2j2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the notch signaling pathway in a hypoxia-induced retinopathy model
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/5e5de2c265c24d939303795672c69e06
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Cytochrome P450 2J2 inhibits the proliferation and angiogenesis of retinal vascular endothelial cells by regulating the Notch signaling pathway in a hypoxia-induced retinopathy model

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