| First Author | Wu D | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 2 | Pages | 2498-2513 |
| PubMed ID | 30277820 | Mgi Jnum | J:286677 |
| Mgi Id | MGI:6388228 | Doi | 10.1096/fj.201801227R |
| Citation | Wu D, et al. (2019) Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition. FASEB J 33(2):2498-2513 |
| abstractText | VEGFA and TGF-beta 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-beta 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-beta1-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. |
