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Inhibition of pathological retinal neovascularization by semaphorin 3A

OBJECTIVE: Pathological retinal angiogenesis is a major cause of vision loss. Semaphorin 3A (Sema3A), a chemorepellent guidance protein, plays crucial roles in neural and vascular patterning. To identify its role in retinal neovascularization, we investigated its antiangiogenic effects. METHODS: Hum...

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Autores principales: Yu, Wenzhen, Bai, Yujing, Han, Na, Wang, Fei, Zhao, Min, Huang, Lvzhen, Li, Xiaoxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695760/
https://www.ncbi.nlm.nih.gov/pubmed/23825919
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author Yu, Wenzhen
Bai, Yujing
Han, Na
Wang, Fei
Zhao, Min
Huang, Lvzhen
Li, Xiaoxin
author_facet Yu, Wenzhen
Bai, Yujing
Han, Na
Wang, Fei
Zhao, Min
Huang, Lvzhen
Li, Xiaoxin
author_sort Yu, Wenzhen
collection PubMed
description OBJECTIVE: Pathological retinal angiogenesis is a major cause of vision loss. Semaphorin 3A (Sema3A), a chemorepellent guidance protein, plays crucial roles in neural and vascular patterning. To identify its role in retinal neovascularization, we investigated its antiangiogenic effects. METHODS: Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study, and an oxygen-induced retinopathy (OIR) mouse model was used for the in vivo study. The HUVECs were incubated with Sema3A, and cell proliferation, migration, apoptosis, cell cycle, tube formation, and c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38 MAPK) signaling pathways were measured using Cell Counting Kit-8, Transwell, flow cytometry, Matrigel assays, and western blot. C57BL/6J mouse pups were exposed to 75% oxygen for 5 days and then brought to room air and injected with Sema3A intravitreously. At postnatal day 18, the retinal nonperfused areas were measured. The in vitro and in vivo vascular endothelial growth factor-165 (VEGF(165)) secretion was measured using enzyme-linked immunosorbent assay. RESULTS: Sema3A not only inhibited VEGF(165)-induced proliferation, but also induced cell cycle arrest in a dose-dependent manner. Furthermore, Sema3A inhibited migration and tube formation, both in general and in VEGF(165)-containing culture medium. Using an enzyme-linked immunosorbent assay, we showed that Sema3A did not affect VEGF(165) secretion, but it did impede VEGF(165) function. Additionally, Sema3A significantly inhibited the phosphorylation of the JNK and p38MAPK signaling pathways. When administered intravitreously, Sema3A reduced the pathological vascular changes seen in the retinal neovascularization OIR model. CONCLUSIONS: These results suggest that the administration of Sema3A could be a useful therapeutic strategy for preventing hypoxia/ischemic-induced retinal neovascularization.
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spelling pubmed-36957602013-07-03 Inhibition of pathological retinal neovascularization by semaphorin 3A Yu, Wenzhen Bai, Yujing Han, Na Wang, Fei Zhao, Min Huang, Lvzhen Li, Xiaoxin Mol Vis Research Article OBJECTIVE: Pathological retinal angiogenesis is a major cause of vision loss. Semaphorin 3A (Sema3A), a chemorepellent guidance protein, plays crucial roles in neural and vascular patterning. To identify its role in retinal neovascularization, we investigated its antiangiogenic effects. METHODS: Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study, and an oxygen-induced retinopathy (OIR) mouse model was used for the in vivo study. The HUVECs were incubated with Sema3A, and cell proliferation, migration, apoptosis, cell cycle, tube formation, and c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38 MAPK) signaling pathways were measured using Cell Counting Kit-8, Transwell, flow cytometry, Matrigel assays, and western blot. C57BL/6J mouse pups were exposed to 75% oxygen for 5 days and then brought to room air and injected with Sema3A intravitreously. At postnatal day 18, the retinal nonperfused areas were measured. The in vitro and in vivo vascular endothelial growth factor-165 (VEGF(165)) secretion was measured using enzyme-linked immunosorbent assay. RESULTS: Sema3A not only inhibited VEGF(165)-induced proliferation, but also induced cell cycle arrest in a dose-dependent manner. Furthermore, Sema3A inhibited migration and tube formation, both in general and in VEGF(165)-containing culture medium. Using an enzyme-linked immunosorbent assay, we showed that Sema3A did not affect VEGF(165) secretion, but it did impede VEGF(165) function. Additionally, Sema3A significantly inhibited the phosphorylation of the JNK and p38MAPK signaling pathways. When administered intravitreously, Sema3A reduced the pathological vascular changes seen in the retinal neovascularization OIR model. CONCLUSIONS: These results suggest that the administration of Sema3A could be a useful therapeutic strategy for preventing hypoxia/ischemic-induced retinal neovascularization. Molecular Vision 2013-06-27 /pmc/articles/PMC3695760/ /pubmed/23825919 Text en Copyright © 2013 Molecular Vision. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yu, Wenzhen
Bai, Yujing
Han, Na
Wang, Fei
Zhao, Min
Huang, Lvzhen
Li, Xiaoxin
Inhibition of pathological retinal neovascularization by semaphorin 3A
title Inhibition of pathological retinal neovascularization by semaphorin 3A
title_full Inhibition of pathological retinal neovascularization by semaphorin 3A
title_fullStr Inhibition of pathological retinal neovascularization by semaphorin 3A
title_full_unstemmed Inhibition of pathological retinal neovascularization by semaphorin 3A
title_short Inhibition of pathological retinal neovascularization by semaphorin 3A
title_sort inhibition of pathological retinal neovascularization by semaphorin 3a
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695760/
https://www.ncbi.nlm.nih.gov/pubmed/23825919
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