title: Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23~27~24 clusters.
abstract: 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∼27∼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.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Qinbo
authors.initials: Q
authors.lastname: Zhou
authors.forename: Rachel
authors.initials: R
authors.lastname: Gallagher
authors.forename: Rafael
authors.initials: R
authors.lastname: Ufret-Vincenty
authors.forename: Xinyu
authors.initials: X
authors.lastname: Li
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Shusheng
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D005810:Multigene Family; D018919:Neovascularization, Physiologic; D012171:Retinal Vessels; D049490:Systems Biology
chemical_list: D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; C529080:Mirn24 microRNA, mouse; C540674:Mirn27 microRNA, mouse