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Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization
Choroidal neovascularization (CNV) is associated with age-related macular degeneration (AMD), a major cause of vision loss among elderly people. Vascular endothelial cell growth factor (VEGF) is essential for the development and progression of AMD, and VEGF signaling molecules are effective targets...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367328/ https://www.ncbi.nlm.nih.gov/pubmed/30733465 http://dx.doi.org/10.1038/s41598-018-38067-4 |
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author | Hayashi, Hisaki Mamun, Abdullah Al Takeyama, Masayuki Yamamura, Aya Zako, Masahiro Yagasaki, Rina Nakahara, Tsutomu Kamei, Motohiro Sato, Motohiko |
author_facet | Hayashi, Hisaki Mamun, Abdullah Al Takeyama, Masayuki Yamamura, Aya Zako, Masahiro Yagasaki, Rina Nakahara, Tsutomu Kamei, Motohiro Sato, Motohiko |
author_sort | Hayashi, Hisaki |
collection | PubMed |
description | Choroidal neovascularization (CNV) is associated with age-related macular degeneration (AMD), a major cause of vision loss among elderly people. Vascular endothelial cell growth factor (VEGF) is essential for the development and progression of AMD, and VEGF signaling molecules are effective targets for the treatment of AMD. We recently reported that activator of G-protein signaling 8 (AGS8), a receptor-independent Gβγ regulator, is involved in VEGF-induced angiogenesis in cultured endothelial cells (EC); however, the role of AGS8 in CNV is not yet understood. This study aimed to explore the role of AGS8 in CNV in cultured cells, explanted choroid tissue, and laser-induced CNV in a mouse AMD model. AGS8 knockdown in cultured choroidal EC inhibited VEGF-induced VEGFR-2 phosphorylation, cell proliferation, and migration. AGS8 knockdown also downregulated cell sprouting from mouse choroidal tissue in ex vivo culture. A mouse model of laser-induced CNV, created to analyze the roles of AGS8 in vivo, demonstrated that AGS8 mRNA was significantly upregulated in choroidal lesions and AGS8 was specifically expressed in the neovasculature. Local AGS8 knockdown in intravitreal tissue significantly inhibited laser-induced AGS8 upregulation and suppressed CNV, suggesting that AGS8 knockdown in the choroid has therapeutic potential for AMD. Together, these results demonstrate that AGS8 plays critical roles in VEGF-induced CNV. |
format | Online Article Text |
id | pubmed-6367328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63673282019-02-11 Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization Hayashi, Hisaki Mamun, Abdullah Al Takeyama, Masayuki Yamamura, Aya Zako, Masahiro Yagasaki, Rina Nakahara, Tsutomu Kamei, Motohiro Sato, Motohiko Sci Rep Article Choroidal neovascularization (CNV) is associated with age-related macular degeneration (AMD), a major cause of vision loss among elderly people. Vascular endothelial cell growth factor (VEGF) is essential for the development and progression of AMD, and VEGF signaling molecules are effective targets for the treatment of AMD. We recently reported that activator of G-protein signaling 8 (AGS8), a receptor-independent Gβγ regulator, is involved in VEGF-induced angiogenesis in cultured endothelial cells (EC); however, the role of AGS8 in CNV is not yet understood. This study aimed to explore the role of AGS8 in CNV in cultured cells, explanted choroid tissue, and laser-induced CNV in a mouse AMD model. AGS8 knockdown in cultured choroidal EC inhibited VEGF-induced VEGFR-2 phosphorylation, cell proliferation, and migration. AGS8 knockdown also downregulated cell sprouting from mouse choroidal tissue in ex vivo culture. A mouse model of laser-induced CNV, created to analyze the roles of AGS8 in vivo, demonstrated that AGS8 mRNA was significantly upregulated in choroidal lesions and AGS8 was specifically expressed in the neovasculature. Local AGS8 knockdown in intravitreal tissue significantly inhibited laser-induced AGS8 upregulation and suppressed CNV, suggesting that AGS8 knockdown in the choroid has therapeutic potential for AMD. Together, these results demonstrate that AGS8 plays critical roles in VEGF-induced CNV. Nature Publishing Group UK 2019-02-07 /pmc/articles/PMC6367328/ /pubmed/30733465 http://dx.doi.org/10.1038/s41598-018-38067-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hayashi, Hisaki Mamun, Abdullah Al Takeyama, Masayuki Yamamura, Aya Zako, Masahiro Yagasaki, Rina Nakahara, Tsutomu Kamei, Motohiro Sato, Motohiko Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization |
title | Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization |
title_full | Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization |
title_fullStr | Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization |
title_full_unstemmed | Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization |
title_short | Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization |
title_sort | activator of g-protein signaling 8 is involved in vegf-induced choroidal neovascularization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367328/ https://www.ncbi.nlm.nih.gov/pubmed/30733465 http://dx.doi.org/10.1038/s41598-018-38067-4 |
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