Please use this identifier to cite or link to this item:
https://doi.org/10.1172/JCI86418
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dc.title | VEGF regulates local inhibitory complement proteins in the eye and kidney | |
dc.contributor.author | Keir, L.S | |
dc.contributor.author | Firth, R | |
dc.contributor.author | Aponik, L | |
dc.contributor.author | Feitelberg, D | |
dc.contributor.author | Sakimoto, S | |
dc.contributor.author | Aguilar, E | |
dc.contributor.author | Welsh, G.I | |
dc.contributor.author | Richards, A | |
dc.contributor.author | Usui, Y | |
dc.contributor.author | Satchell, S.C | |
dc.contributor.author | Kuzmuk, V | |
dc.contributor.author | Coward, R.J | |
dc.contributor.author | Goult, J | |
dc.contributor.author | Bull, K.R | |
dc.contributor.author | Sharma, R | |
dc.contributor.author | Bharti, K | |
dc.contributor.author | Westenskow, P.D | |
dc.contributor.author | Michael, I.P | |
dc.contributor.author | Saleem, M.A | |
dc.contributor.author | Friedlander, M | |
dc.date.accessioned | 2020-10-23T02:36:34Z | |
dc.date.available | 2020-10-23T02:36:34Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Keir, L.S, Firth, R, Aponik, L, Feitelberg, D, Sakimoto, S, Aguilar, E, Welsh, G.I, Richards, A, Usui, Y, Satchell, S.C, Kuzmuk, V, Coward, R.J, Goult, J, Bull, K.R, Sharma, R, Bharti, K, Westenskow, P.D, Michael, I.P, Saleem, M.A, Friedlander, M (2017). VEGF regulates local inhibitory complement proteins in the eye and kidney. Journal of Clinical Investigation 127 (1) : 199-214. ScholarBank@NUS Repository. https://doi.org/10.1172/JCI86418 | |
dc.identifier.issn | 0021-9738 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/179248 | |
dc.description.abstract | Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPEand podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-?/CREB signaling. Patient podocytes and RPE cells carrying diseaseassociated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF inhibition could reduce cellular complement regulatory capacity. VEGF antagonism also increased markers of endothelial cell activation, which was partially reduced by genetic complement inhibition. Together, these results suggest that VEGF protects the retinal and glomerular microvasculature, not only through VEGFR2-mediated vasculotrophism, but also through modulation of local complement proteins that could protect against complement-mediated damage. Though further study is warranted, these findings could be relevant for patients receiving VEGF antagonists. | |
dc.publisher | American Society for Clinical Investigation | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | complement | |
dc.subject | complement factor H | |
dc.subject | vasculotropin | |
dc.subject | vasculotropin receptor 2 | |
dc.subject | complement factor H | |
dc.subject | CREB1 protein, human | |
dc.subject | Creb1 protein, mouse | |
dc.subject | cyclic AMP responsive element binding protein | |
dc.subject | eye protein | |
dc.subject | KDR protein, human | |
dc.subject | Kdr protein, mouse | |
dc.subject | PRKCA protein, human | |
dc.subject | Prkca protein, mouse | |
dc.subject | protein kinase C alpha | |
dc.subject | vascular endothelial growth factor A, mouse | |
dc.subject | vasculotropin A | |
dc.subject | vasculotropin receptor 2 | |
dc.subject | VEGFA protein, human | |
dc.subject | age related macular degeneration | |
dc.subject | Article | |
dc.subject | choroid disease | |
dc.subject | comparative study | |
dc.subject | complement activation | |
dc.subject | complement alternative pathway | |
dc.subject | complement deposition | |
dc.subject | complement inhibition | |
dc.subject | controlled study | |
dc.subject | CRISPR Cas system | |
dc.subject | enzyme linked immunosorbent assay | |
dc.subject | epithelium cell | |
dc.subject | eye | |
dc.subject | genetic variability | |
dc.subject | HEK293 cell line | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | immunofluorescence | |
dc.subject | kidney | |
dc.subject | microvasculature | |
dc.subject | neovascularization (pathology) | |
dc.subject | podocyte | |
dc.subject | priority journal | |
dc.subject | retinal pigment epithelium | |
dc.subject | thrombotic thrombocytopenic purpura | |
dc.subject | umbilical vein endothelial cell | |
dc.subject | Western blotting | |
dc.subject | aged | |
dc.subject | animal | |
dc.subject | antagonists and inhibitors | |
dc.subject | female | |
dc.subject | genetics | |
dc.subject | kidney disease | |
dc.subject | knockout mouse | |
dc.subject | macular degeneration | |
dc.subject | male | |
dc.subject | metabolism | |
dc.subject | mouse | |
dc.subject | pathology | |
dc.subject | Aged | |
dc.subject | Animals | |
dc.subject | Complement Factor H | |
dc.subject | Cyclic AMP Response Element-Binding Protein | |
dc.subject | Eye Proteins | |
dc.subject | Female | |
dc.subject | Humans | |
dc.subject | Kidney Diseases | |
dc.subject | Macular Degeneration | |
dc.subject | Male | |
dc.subject | Mice | |
dc.subject | Mice, Knockout | |
dc.subject | Podocytes | |
dc.subject | Protein Kinase C-alpha | |
dc.subject | Retinal Pigment Epithelium | |
dc.subject | Thrombotic Microangiopathies | |
dc.subject | Vascular Endothelial Growth Factor A | |
dc.subject | Vascular Endothelial Growth Factor Receptor-2 | |
dc.type | Article | |
dc.contributor.department | MEDICINE | |
dc.description.doi | 10.1172/JCI86418 | |
dc.description.sourcetitle | Journal of Clinical Investigation | |
dc.description.volume | 127 | |
dc.description.issue | 1 | |
dc.description.page | 199-214 | |
dc.published.state | Published | |
Appears in Collections: | Elements Staff Publications |
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