Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization
| Autor: | Masahiro Zako, Motohiro Kamei, Rina Yagasaki, Aya Yamamura, Tsutomu Nakahara, Hisaki Hayashi, Motohiko Sato, Abdullah Al Mamun, Masayuki Takeyama |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine genetic structures Angiogenesis Cell Gene Expression lcsh:Medicine Article Cell Line Macular Degeneration Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals RNA Small Interfering lcsh:Science Cells Cultured Gene knockdown Multidisciplinary Activator (genetics) Cell growth business.industry lcsh:R Intracellular Signaling Peptides and Proteins Endothelial Cells Macaca mulatta Choroidal Neovascularization eye diseases Disease Models Animal 030104 developmental biology Choroidal neovascularization medicine.anatomical_structure Cancer research lcsh:Q Disease Susceptibility sense organs medicine.symptom business 030217 neurology & neurosurgery Ex vivo |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-38067-4 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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