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Open AccessArticle

Effects of FTMT Expression by Retinal Pigment Epithelial Cells on Features of Angiogenesis

Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
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Int. J. Mol. Sci. 2020, 21(10), 3635; https://doi.org/10.3390/ijms21103635
Received: 24 April 2020 / Revised: 19 May 2020 / Accepted: 19 May 2020 / Published: 21 May 2020
(This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration (AMD) 2.0)
Aberrant angiogenesis is a pathological feature of a number of diseases and arises from the uncoordinated expression of angiogenic factors as response to different cellular stresses. Age-related macular degeneration (AMD), a leading cause of vision loss, can result from pathological angiogenesis. As a mutation in the mitochondrial ferritin (FTMT) gene has been associated with AMD, its possible role in modulating angiogenic factors and angiogenesis was investigated. FTMT is an iron-sequestering protein primarily expressed in metabolically active cells and tissues with high oxygen demand, including retina. In this study, we utilized the human retinal pigment epithelial cell line ARPE-19, both as undifferentiated and differentiated cells. The effects of proinflammatory cytokines, FTMT knockdown, and transient and stable overexpression of FTMT were investigated on expression of pro-angiogenic vascular endothelial growth factor (VEGF) and anti-angiogenic pigment epithelial-derived factor (PEDF). Proinflammatory cytokines induced FTMT and VEGF expression, while NF-κB inhibition significantly reduced FTMT expression. VEGF protein and mRNA expression were significantly increased in FTMT-silenced ARPE-19 cells. Using an in vitro angiogenesis assay with endothelial cells, we showed that conditioned media from FTMT-overexpressing cells had significant antiangiogenic effects. Collectively, our findings indicate that increased levels of FTMT inhibit angiogenesis, possibly by reducing levels of VEGF and increasing PEDF expression. The cellular models developed can be used to investigate if increased FTMT may be protective in angiogenic diseases, such as AMD. View Full-Text
Keywords: mitochondrial ferritin; vascular endothelial growth factor; angiogenesis; retinal pigment epithelium; age-related macular degeneration; differentiation mitochondrial ferritin; vascular endothelial growth factor; angiogenesis; retinal pigment epithelium; age-related macular degeneration; differentiation
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MDPI and ACS Style

Buyandelger, U.; Walker, D.G.; Yanagisawa, D.; Morimura, T.; Tooyama, I. Effects of FTMT Expression by Retinal Pigment Epithelial Cells on Features of Angiogenesis. Int. J. Mol. Sci. 2020, 21, 3635.

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