Laboratory of Ocular Cell Biology and Visual Science, Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
FASEB J. 2019 Feb;33(2):2498-2513. doi: 10.1096/fj.201801227R. Epub 2018 Oct 2.
VEGFA and TGF-β 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-β 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-β1-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.
VEGFA 和 TGF-β 是已知的主要血管生成和纤维化因子。半乳糖凝集素-1（由凝集素、半乳糖结合、可溶性（LGALS）1 编码）因其在血管生成和纤维化中的促进作用而引起了越来越多的关注，其通过修饰 VEGFA 和 TGF-β 受体信号通路来实现。我们揭示了半乳糖凝集素-1 参与了激光诱导的脉络膜新生血管（CNV）和视网膜下纤维化的小鼠模型，这两者都代表了年龄相关性黄斑变性（AMD）的发病机制。Lgals1 的缺失或过表达都不会影响生理视网膜发育或视觉功能。Galectin-1/Lgals1 在内皮细胞中的表达在 CNV 诱导时上调，而 Lgals1 的缺失则抑制了 CNV 以及 VEGFR2 的下游分子。Lgals1 的缺失也减弱了视网膜下纤维化、上皮-间充质转化（EMT）标志物包括 Snai1 的表达以及 SMAD 家族成员 2 的磷酸化。支持这些体内发现，人视网膜色素上皮（RPE）细胞中 LGALS1 的沉默抑制了 TGF-β1 诱导的 EMT 相关分子和细胞迁移能力。相反，Lgals1 的过表达增强了 CNV 和视网膜下纤维化。AMD 患者的标本显示，半乳糖凝集素-1 与血管内皮细胞中的 VEGFR2 以及 RPE 细胞中的磷酸化 SMAD2 共定位。这些结果表明半乳糖凝集素-1 作为 AMD 眼中血管生成和纤维化的关键促进剂具有重要的生物学意义。
