Overexpression of miR‐181a‐5p inhibits retinal neovascularization through endocan and the ERK1/2 signaling pathway
Open Access
- 28 April 2020
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 235 (12), 9323-9335
- https://doi.org/10.1002/jcp.29733
Abstract
Retinal neovascularization (RNV) is a common pathological feature of angiogenesis‐related retinopathy. Endocan inhibition has previously been reported to suppress RNV in oxygen‐induced retinopathy (OIR); however, its molecular mechanisms remain to be elucidated. Here, we investigated the role and mechanism of endocan in OIR. We established an OIR mouse model and detected aberrant endocan overexpression in OIR mouse retinas. Endocan inhibition through small interfering RNA or a neutralizing antibody inhibited vascular endothelial growth factor‐induced cell survival, cell proliferation, and tube formation in human retinal endothelial cells in vitro and reduced the RNV area in vivo. Using RNA sequencing, a luciferase reporter assay, and bioinformatics analyses, we identified endocan as a microRNA‐181a‐5p target gene. The antiangiogenic effect of miR‐181a‐5p on RNV was verified by intravitreal injection, and we showed that this involved the extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) signaling pathway. Collectively, our data demonstrate that miR‐181a‐5p/endocan regulates retinal angiogenesis through the ERK1/2 signaling pathway and might represent an attractive therapeutic strategy for RNV.Keywords
Funding Information
- National Natural Science Foundation of China (81641157, 81800843)
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