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MicroRNA Expression Profiles of Human iPS Cells, Retinal Pigment Epithelium Derived From iPS, and Fetal Retinal Pigment Epithelium
Published on: June 24, 2014
MicroRNA-27a protects retinal pigment epithelial cells under high glucose conditions by targeting TLR4
Xiaolei Tang1, Yan Dai1, Xiaoli Wang1
1Department of Ophthalmology, Mianyang Central Hospital, Mianyang, Sichuan 621000, P.R. China.
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-1β, tumor necrosis factor (TNF)-α 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-1β and TNF-α, 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.
Insights
MicroRNA-27a (miRNA27a) protects retinal cells from high glucose damage by reducing inflammation and apoptosis. This involves targeting Toll-like receptor 4 (TLR4), offering a potential therapeutic avenue for diabetic retinopathy.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- The pathogenesis of DR involves retinal pigment epithelial (RPE) cell damage.
- MicroRNAs play critical roles in cellular processes and disease development.
Purpose of the Study:
- To investigate the role of microRNA-27a (miRNA27a) in diabetic retinopathy pathogenesis.
- To elucidate the molecular mechanism of miRNA27a in high glucose-induced RPE cell injury.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to measure miRNA27a expression.
- Assays for caspase-3/9 activity, B-cell lymphoma 2-associated X (Bax) protein expression, and cell viability.
- Inhibition of miRNA27a and treatment with immunostimulatory RNA (isRNA) targeting Toll-like receptor 4 (TLR4).
Main Results:
- High glucose decreased miRNA27a expression in RPE cells.
- Inhibition of miRNA27a exacerbated high glucose-induced RPE cell apoptosis and inflammation.
- Targeting TLR4 with isRNA reversed the detrimental effects of miRNA27a inhibition under high glucose conditions.
Conclusions:
- miRNA27a protects RPE cells against high glucose-induced damage.
- The protective mechanism involves the inhibition of inflammation and apoptosis via targeting TLR4.
- miRNA27a represents a potential therapeutic target for diabetic retinopathy.
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