MicroRNA-184 modulates canonical Wnt signaling through the regulation of frizzled-7 expression in the retina with ischemia-induced neovascularization

•MiR-184 is down-regulated in the retina of OIR mice.•Canonical Wnt signaling is regulated by miR-184.•Fzd7 is a downstream target of miR-184.•Delivery of precursor of miR-184 inhibits Wnt signaling in the retina of OIR mice. Aberrant activation of Wnt signaling contributes to ischemia-induced retin...

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Bibliographic Details
Published in:FEBS letters 2015-04, Vol.589 (10), p.1143-1149
Main Authors: Takahashi, Yusuke, Chen, Qian, Rajala, Raju V.S., Ma, Jian-xing
Format: Article
Language:English
Subjects:
3′ un-translated region
3′UTR
Animals
diabetic retinopathy
frizzled-7
Fzd7
Gene delivery
Gfap
glial fibrillary acidic protein
Hprt1
hypoxanthine phosphoribosyltransferase 1
Ischemia - genetics
Ischemia - metabolism
Ischemia - pathology
Mice
Mice, Transgenic
MicroRNA
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Neovascularization
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
OIR
Oxygen-induced retinopathy
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
Retina - metabolism
Retina - pathology
T-cell factor/lymphoid enhancing factor
TCF/LEF
vascular endothelial growth factor-a
Vegf-a
Wnt Signaling Pathway
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Summary:•MiR-184 is down-regulated in the retina of OIR mice.•Canonical Wnt signaling is regulated by miR-184.•Fzd7 is a downstream target of miR-184.•Delivery of precursor of miR-184 inhibits Wnt signaling in the retina of OIR mice. Aberrant activation of Wnt signaling contributes to ischemia-induced retinal neovascularization in oxygen-induced retinopathy (OIR), although the underlying mechanism is so far unclear. Here, we show that microRNA-184 (miR-184) is significantly down-regulated in the retina of OIR mice, and miR-184 negatively modulates Wnt signaling both in vivo and in vitro. Furthermore, we show that the Wnt receptor, frizzled-7, is a downstream target of miR-184, and delivery of miR-184 mimic inhibits Wnt signaling in the OIR retina. These results suggest that decreased levels of miR-184 are responsible, at least in part, for the aberrant activation of Wnt signaling in ischemia-induced retinal neovascularization.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2015.03.010