MicroRNA-384-3p inhibits retinal neovascularization through targeting hexokinase 2 in mice with diabetic retinopathy.
J Cell Physiol
; 234(1): 721-730, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-30191948
ABSTRACT
Diabetic retinopathy (DR) presents a microvascular complication of diabetes, which may contribute to visual impairment. The treatment of DR is still controversial. Accumulating studies have reported the role of microRNAs (miRs) in DR. This study aims to explore the functions of microRNA-384-3p (miR-384-3p) in retinal neovascularization by targeting hexokinase 2 (HK2) in mice with DR. A total of 43 C57BL/6 male mice were selected and divided into normal ( n = 16) and DR ( n = 27) groups. Retinal microvascular endothelial cells (RMECs) were collected from the normal and DR mice and mainly treated with a miR-384-3p mimic, a miR-384-3p inhibitor, small interfering RNA (siRNA) against HK2 and HK2 overexpression plasmids to understand the underlying regulatory mechanisms of miR-384-3p. The relationship between miR-384-3p and HK2 was determined by dual-luciferase reporter assay. The miR-384-3p expression and the mRNA and the protein expressions of HK2 and CD31 in retinal tissues and cells were evaluated using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tube formation was observed by conducting a tube formation experiment. HK2 is a target gene of miR-384-3p. The DR mice showed higher expression of HK2 and CD31 but lower expression of miR-384-3p. The miR-384-3p mimic and siRNA-HK2 reduced the expression of HK2, decreased cell proliferation and tube formation of RMECs, whereas the miR-384-3p inhibitor could reverse these trends. Our study demonstrates that overexpression of miR-384-3p inhibits retinal neovascularization in DR mice via inhibition of HK2.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neovascularização Retiniana
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MicroRNAs
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Retinopatia Diabética
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Hexoquinase
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article