RRC ID 60122
Author Hayashi H, Mamun AA, Takeyama M, Yamamura A, Zako M, Yagasaki R, Nakahara T, Kamei M, Sato M.
Title Activator of G-protein signaling 8 is involved in VEGF-induced choroidal neovascularization.
Journal Sci Rep
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.
Volume 9(1)
Pages 1560
Published 2019-2-7
DOI 10.1038/s41598-018-38067-4
PII 10.1038/s41598-018-38067-4
PMID 30733465
PMC PMC6367328
MeSH Animals Cell Line Cells, Cultured Choroidal Neovascularization / etiology* Choroidal Neovascularization / metabolism* Choroidal Neovascularization / pathology Disease Models, Animal Disease Susceptibility Endothelial Cells / metabolism Gene Expression Intracellular Signaling Peptides and Proteins / genetics* Intracellular Signaling Peptides and Proteins / metabolism Macaca mulatta Macular Degeneration / etiology Macular Degeneration / metabolism Macular Degeneration / pathology Male Mice RNA, Small Interfering / genetics Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor A / metabolism*
IF 4.011
Times Cited 1
Human and Animal Cells RF/6A 135(RCB1556)