let-7 Contributes to Diabetic Retinopathy but Represses Pathological Ocular Angiogenesis
| Autor: | Qinbo Zhou, Fangkun Zhao, Chastain Anderson, Shusheng Wang, Jing Ma, Robert J. A. Frost, Bo Yu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Angiogenesis Transgene Cell Biology Diabetic retinopathy Macular degeneration Biology medicine.disease eye diseases Neovascularization Pathogenesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Choroidal neovascularization 030221 ophthalmology & optometry Cancer research medicine Gene silencing sense organs medicine.symptom Molecular Biology Research Article |
| Zdroj: | Molecular and Cellular Biology. 37 |
| ISSN: | 1098-5549 |
| Popis: | The in vivo function of microRNAs (miRs) in diabetic retinopathy (DR) and age-related macular degeneration (AMD) remains unclear. We report here that let-7 family members are expressed in retinal and choroidal endothelial cells (ECs). In ECs, overexpression of let-7 by adenovirus represses EC proliferation, migration, and networking in vitro, whereas inhibition of the let-7 family with a locked nucleic acid (LNA)–anti-miR has the opposite effect. Mechanistically, silencing of the let-7 target HMGA2 gene mimics the phenotype of let-7 overexpression in ECs. let-7 transgenic (let-7-Tg) mice show features of nonproliferative DR, including tortuous retinal vessels and defective pericyte coverage. However, these mice develop significantly less choroidal neovascularization (CNV) compared to wild-type controls after laser injury. Consistently, silencing of let-7 in the eye increased laser-induced CNV in wild-type mice. Together, our data establish a causative role of let-7 in nonproliferative diabetic retinopathy and a repressive function of let-7 in pathological angiogenesis, suggesting distinct implications of let-7 in the pathogenesis of DR and AMD. |
| Databáze: | OpenAIRE |
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