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MicroRNA-27a protects retinal pigment epithelial cells under high glucose conditions by targeting TLR4.

ABSTRACT: The present study aimed to investigate whether microRNA-27a (miRNA27a) is associated with the pathogenesis of diabetic retinopathy, and to elucidate the underlying molecular mechanism of any potential association. In retinal pigment epithelial (RPE) cells treated with high glucose, miRNA27a expression, determined by reverse transcription-quantitative polymerase chain reaction analysis, was decreased. Caspase-3/9 activity and B-cell lymphoma 2-associated X (Bax) protein expression was increased in RPE cells subjected to high glucose. Inhibition of miRNA27a suppressed the viability, and increased the caspase-3/9 activity and Bax protein expression of RPE cells treated with high glucose. Inhibition of miRNA27a expression also increased the expression of interleukin (IL)-6, IL-1?, tumor necrosis factor (TNF)-? and Toll-like receptor 4 (TLR4) in RPE cells treated with high glucose. Treatment with immunostimulatory (is)RNA directed against TLR4 was observed to inhibit caspase-3/9 activity, decrease the expression of TLR4, Bax, IL-6, IL-1? and TNF-?, and increase the viability of RPE cells subjected to high glucose following the inhibition miRNA27a. In conclusion, the results of the present study suggest that miRNA27a protects RPE cells subjected to high glucose via inhibiting inflammation and apoptosis through targeting TLR4.

SUBMITTER: Tang X

PROVIDER: S-EPMC5995053 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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MicroRNA-27a protects retinal pigment epithelial cells under high glucose conditions by targeting TLR4.

Tang Xiaolei X Dai Yan Y Wang Xiaoli X Zeng Jian J Li Guirong G

Experimental and therapeutic medicine 20180510 1

The present study aimed to investigate whether microRNA-27a (miRNA27a) is associated with the pathogenesis of diabetic retinopathy, and to elucidate the underlying molecular mechanism of any potential association. In retinal pigment epithelial (RPE) cells treated with high glucose, miRNA27a expression, determined by reverse transcription-quantitative polymerase chain reaction analysis, was decreased. Caspase-3/9 activity and B-cell lymphoma 2-associated X (Bax) protein expression was increased i ...[more]

PMID: 29896271

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Project description:Background:Proliferative vitreoretinopathy (PVR) is a severe blinding complication of retinal detachment surgery. Increasing evidence demonstrate that PVR is associated with oxidative stress. Scutellarin is a natural flavone compound that has been reported to have anti-oxidative activity. However, the effect of scutellarin on PVR remains unknown. In the current study, we assessed the effect of scutellarin on hydrogen peroxide (H2O2)-induced oxidative injury in human retinal pigment epithelium cells (ARPE-19). Methods:ARPE-19 cells were pretreated with different concentrations of scutellarin for 2 h, and then challenged with H2O2 (1 mM) for 24 h. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) and glutathione (GSH) activity were measured to assess the level of oxidative stress. Flow cytometry was performed to detect the apoptosis rate of ARPE-19 cells. Expression levels of bcl-2, bax, cleaved-caspase-3, p-JAK2, JAK2, p-STAT3, and STAT3 were measured using western blot. Results:Our results revealed that scutellarin improved the cell viability of H2O2-induced ARPE-19 cells. Scutellarin alleviated the H2O2-induced oxidative stress in ARPE-19 cells, which was illustrated by reduced levels of ROS and MDA, accompanied by increased SOD activity and GSH level. The increased apoptosis rate of ARPE-19 cells caused by H2O2 induction was significantly decreased after scutellarin treatment. H2O2 treatment resulted in significant increase in bax expression and decrease in bcl-2 expression, while the changes in the expressions of bax and bcl-2 were reversed by scutellarin treatment. In addition, scutellarin promoted the activation of JAK2/STAT3 signaling pathway in H2O2-induced ARPE-19 cells. Suppression of JAK2/STAT3 signaling pathway abolished the protective effects of scutellarin on H2O2-induced ARPE-19 cells. Conclusion:These findings suggested that scutellarin was capable for alleviating H2O2-induced oxidative damage in ARPE-19 cells, which might be ascribed to the activation of JAK2/STAT3 signaling pathway.

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MicroRNA-27a protects retinal pigment epithelial cells under high glucose conditions by targeting TLR4.

Publications

MicroRNA-27a protects retinal pigment epithelial cells under high glucose conditions by targeting TLR4.

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