Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition.
FASEB J
; 33(2): 2498-2513, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30277820
ABSTRACT
VEGFA and TGF-ß are known major angiogenic and fibrogenic factors. Galectin-1, encoded by lectin, galactoside-binding, soluble ( LGALS) 1, has attracted growing attention for its facilitatory role in angiogenesis and fibrosis through its modification of VEGFA and TGF-ß receptor signaling pathways. We reveal galectin-1 involvement in the mouse model of laser-induced choroidal neovascularization (CNV) and subretinal fibrosis, both of which represent the pathogenesis of age-related macular degeneration (AMD). Neither deletion nor overexpression of Lgals1 affected physiologic retinal development or visual function. Galectin-1/ Lgals1 was upregulated by CNV induction, whereas deletion of Lgals1 suppressed CNV together with downstream molecules of VEGF receptor (VEGFR)2. Loss of Lgals1 also attenuated subretinal fibrosis, expression of epithelial-mesenchymal transition (EMT) markers including Snai1, and phosphorylation of SMAD family member 2. Supporting these in vivo findings, silencing of LGALS1 in human retinal pigment epithelial (RPE) cells inhibited TGF-ß1-induced EMT-related molecules and cell motilities. Conversely, overexpression of Lgals1 enhanced CNV and subretinal fibrosis. Specimens from patients with AMD demonstrated colocalization of galectin-1 with VEGFR2 in neovascular endothelial cells and with phosphorylated SMAD2 in RPE cells. These results suggested a biologic significance of galectin-1 as a key promotor for both angiogenesis and fibrosis in eyes with AMD.-Wu, D., Kanda, A., Liu, Y., Kase, S., Noda, K., Ishida, S. Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Retina
/
Fibrose
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Neovascularização de Coroide
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Galectina 1
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Epitélio Pigmentado da Retina
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Transição Epitelial-Mesenquimal
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Degeneração Macular
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Aged80
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Animals
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Female
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Humans
/
Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article