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...
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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. |
doi_str_mv | 10.1038/s41598-018-38067-4 |
format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-38067-4</identifier><identifier>PMID: 30733465</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/106 ; 13/31 ; 13/95 ; 14/63 ; 38/90 ; 42/89 ; 631/443/7 ; 631/80/86 ; 64/60 ; 82/51 ; Age ; Angiogenesis ; Animals ; Cell culture ; Cell growth ; Cell Line ; Cell migration ; Cell proliferation ; Cells, Cultured ; Choroidal Neovascularization - etiology ; Choroidal Neovascularization - metabolism ; Choroidal Neovascularization - pathology ; Disease Models, Animal ; Disease Susceptibility ; Endothelial cells ; Endothelial Cells - metabolism ; Gene Expression ; Geriatrics ; Humanities and Social Sciences ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; Lasers ; Macaca mulatta ; Macular degeneration ; Macular Degeneration - etiology ; Macular Degeneration - metabolism ; Macular Degeneration - pathology ; Male ; Mice ; mRNA ; multidisciplinary ; Phosphorylation ; RNA, Small Interfering - genetics ; Science ; Science (multidisciplinary) ; Tissue culture ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism ; Vascular endothelial growth factor receptors ; Vascularization</subject><ispartof>Scientific reports, 2019-02, Vol.9 (1), p.1560, Article 1560</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-8eeac568de2170b3deb7945fc75e9c7e8190530fe388bbc72fd6f2fbae74bbe43</citedby><cites>FETCH-LOGICAL-c540t-8eeac568de2170b3deb7945fc75e9c7e8190530fe388bbc72fd6f2fbae74bbe43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367328/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367328/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30733465$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hayashi, Hisaki</creatorcontrib><creatorcontrib>Mamun, Abdullah Al</creatorcontrib><creatorcontrib>Takeyama, Masayuki</creatorcontrib><creatorcontrib>Yamamura, Aya</creatorcontrib><creatorcontrib>Zako, Masahiro</creatorcontrib><creatorcontrib>Yagasaki, Rina</creatorcontrib><creatorcontrib>Nakahara, Tsutomu</creatorcontrib><creatorcontrib>Kamei, Motohiro</creatorcontrib><creatorcontrib>Sato, Motohiko</creatorcontrib><title>Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><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.</description><subject>13</subject><subject>13/106</subject><subject>13/31</subject><subject>13/95</subject><subject>14/63</subject><subject>38/90</subject><subject>42/89</subject><subject>631/443/7</subject><subject>631/80/86</subject><subject>64/60</subject><subject>82/51</subject><subject>Age</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Cells, Cultured</subject><subject>Choroidal Neovascularization - etiology</subject><subject>Choroidal Neovascularization - metabolism</subject><subject>Choroidal Neovascularization - pathology</subject><subject>Disease Models, Animal</subject><subject>Disease Susceptibility</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - metabolism</subject><subject>Gene Expression</subject><subject>Geriatrics</subject><subject>Humanities and Social Sciences</subject><subject>Intracellular Signaling Peptides and Proteins - 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etiology</topic><topic>Choroidal Neovascularization - metabolism</topic><topic>Choroidal Neovascularization - pathology</topic><topic>Disease Models, Animal</topic><topic>Disease Susceptibility</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - metabolism</topic><topic>Gene Expression</topic><topic>Geriatrics</topic><topic>Humanities and Social Sciences</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Lasers</topic><topic>Macaca mulatta</topic><topic>Macular degeneration</topic><topic>Macular Degeneration - etiology</topic><topic>Macular Degeneration - metabolism</topic><topic>Macular Degeneration - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>mRNA</topic><topic>multidisciplinary</topic><topic>Phosphorylation</topic><topic>RNA, Small Interfering - genetics</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Tissue culture</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Vascular endothelial growth factor receptors</topic><topic>Vascularization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hayashi, Hisaki</creatorcontrib><creatorcontrib>Mamun, Abdullah Al</creatorcontrib><creatorcontrib>Takeyama, Masayuki</creatorcontrib><creatorcontrib>Yamamura, Aya</creatorcontrib><creatorcontrib>Zako, Masahiro</creatorcontrib><creatorcontrib>Yagasaki, Rina</creatorcontrib><creatorcontrib>Nakahara, Tsutomu</creatorcontrib><creatorcontrib>Kamei, Motohiro</creatorcontrib><creatorcontrib>Sato, Motohiko</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hayashi, Hisaki</au><au>Mamun, Abdullah Al</au><au>Takeyama, Masayuki</au><au>Yamamura, Aya</au><au>Zako, Masahiro</au><au>Yagasaki, Rina</au><au>Nakahara, Tsutomu</au><au>Kamei, Motohiro</au><au>Sato, Motohiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-02-07</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>1560</spage><pages>1560-</pages><artnum>1560</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30733465</pmid><doi>10.1038/s41598-018-38067-4</doi><oa>free_for_read</oa></addata></record> |
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subjects | 13 13/106 13/31 13/95 14/63 38/90 42/89 631/443/7 631/80/86 64/60 82/51 Age Angiogenesis Animals Cell culture Cell growth Cell Line Cell migration Cell proliferation Cells, Cultured Choroidal Neovascularization - etiology Choroidal Neovascularization - metabolism Choroidal Neovascularization - pathology Disease Models, Animal Disease Susceptibility Endothelial cells Endothelial Cells - metabolism Gene Expression Geriatrics Humanities and Social Sciences Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism Lasers Macaca mulatta Macular degeneration Macular Degeneration - etiology Macular Degeneration - metabolism Macular Degeneration - pathology Male Mice mRNA multidisciplinary Phosphorylation RNA, Small Interfering - genetics Science Science (multidisciplinary) Tissue culture Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism Vascular endothelial growth factor receptors Vascularization |
title | Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization |
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