期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 20, 页码 8287-8292出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1105254108
关键词
blindness; MAP kinase signaling; semaphorins; Akt; proangiogenic
资金
- Department of Ophthalmology at UT Southwestern Medical Center
- National Institutes of Health [EY020799]
- Research to Prevent Blindness
- Donald W. Reynolds Center for Clinical Cardiovascular Research
- Robert A. Welch Foundation [I-0025]
- Foundation Leducq's Transatlantic Network of Excellence in Cardiovascular Research Program
- American Heart Association
- Jon Holden DeHaan Foundation
MicroRNAs (miRNAs) modulate complex physiological and pathological processes by repressing expression of multiple components of cellular regulatory networks. Here we demonstrate that miRNAs encoded by the miR-23 similar to 27 similar to 24 gene clusters are enriched in endothelial cells and highly vascularized tissues. Inhibition of miR-23 and miR-27 function by locked nucleic acid-modified anti-miRNAs represses angiogenesis in vitro and postnatal retinal vascular development in vivo. Moreover, miR-23 and miR-27 are required for pathological angiogenesis in a laser-induced choroidal neovascularization mouse model. MiR-23 and miR-27 enhance angiogenesis by promoting angiogenic signaling through targeting Sprouty2 and Sema6A proteins, which exert antiangiogenic activity. Manipulating miR-23/27 levels may have important therapeutic implications in neovascular age-related macular degeneration and other vascular disorders.
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