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Effects of FTMT Expression by Retinal Pigment Epithelial Cells on Features of Angiogenesis.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 May 21; Vol. 21 (10). Date of Electronic Publication: 2020 May 21. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Cell Line
Cytokines genetics
Cytokines metabolism
Eye Proteins genetics
Eye Proteins metabolism
Ferritins genetics
Humans
Mitochondrial Proteins genetics
NF-kappa B genetics
NF-kappa B metabolism
Nerve Growth Factors genetics
Nerve Growth Factors metabolism
Retinal Pigment Epithelium cytology
Serpins genetics
Serpins metabolism
Vascular Endothelial Growth Factor A genetics
Vascular Endothelial Growth Factor A metabolism
Ferritins metabolism
Mitochondrial Proteins metabolism
Neovascularization, Physiologic
Retinal Pigment Epithelium metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32455741
- Full Text :
- https://doi.org/10.3390/ijms21103635