1. SNAI1, an endothelial-mesenchymal transition transcription factor, promotes the early phase of ocular neovascularization.
- Author
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Sun JX, Chang TF, Li MH, Sun LJ, Yan XC, Yang ZY, Liu Y, Xu WQ, Lv Y, Su JB, Liang L, Han H, Dou GR, and Wang YS
- Subjects
- Animals, Cell Movement genetics, Cytoskeleton genetics, Cytoskeleton metabolism, Extracellular Matrix genetics, Extracellular Matrix metabolism, Gene Expression Regulation, Human Umbilical Vein Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells pathology, Humans, Male, Mice, Neovascularization, Pathologic genetics, Neovascularization, Pathologic metabolism, Neovascularization, Pathologic pathology, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Retina metabolism, Retina pathology, Retinal Neovascularization genetics, Retinal Neovascularization pathology, Retinal Vessels metabolism, Retinal Vessels pathology, Sequence Analysis, RNA, Snail Family Transcription Factors genetics, Neovascularization, Pathologic physiopathology, Retina physiopathology, Retinal Neovascularization physiopathology, Retinal Vessels physiopathology, Snail Family Transcription Factors metabolism
- Abstract
Ocular neovascularization is a comprehensive process involved in retinal vascular development and several blinding diseases such as age-related macular degeneration and retinopathy of prematurity, with vascular endothelial growth factor (VEGF) regarded as the master regulator. However, the qualified effect of anti-VEGF therapy reveals that the underlying mechanisms are still not clearly identified. To initialize angiogenesis, endothelial cells undergo a phenotype switching to generate highly migratory and invasive cells. This process shares certain similar characters observed in endothelial-mesenchymal transition (EndMT). Here, we found that SNAI1, an EndMT transcription factor, was expressed by endothelial cells in both physiological and pathological ocular neovascularization. SNAI1 overexpression triggered cell morphological change and enhanced cell motility, while loss of SNAI1 attenuated migration, invasion and sprouting. RNA sequence analysis further revealed that SNAI1 knockdown decreased the expression of genes related to cytoskeleton rearrangement and ECM remodeling. Moreover, intravitreal injection of small interfering RNA of SNAI1 suppressed new vessel formation in developing retina as well as mice model of choroidal neovascularization and oxygen-induced retinopathy. Therefore, we propose that the EndMT transcription factor SNAI1 promotes the early phase of ocular neovascularization and may provide a potential therapeutic target.
- Published
- 2018
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