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Overexpression of miR‐181a‐5p inhibits retinal neovascularization through endocan and the ERK1/2 signaling pathway
Author(s) -
Chen Xiuping,
Yao Yiyun,
Yuan Fei,
Xie Bing
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29733
Subject(s) - angiogenesis , retinal , small interfering rna , microbiology and biotechnology , signal transduction , neovascularization , microrna , mapk/erk pathway , kinase , vascular endothelial growth factor a , vascular endothelial growth factor , cancer research , biology , chemistry , transfection , cell culture , biochemistry , gene , vegf receptors , genetics
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.