LIN28A Attenuates High Glucose-induced Retinal Pigmented Epithelium Injury Through Activating SIRT1-dependent Autophagy

Overview

Journal Int J Ophthalmol

Specialty Ophthalmology

Date 2023 Sep 19

PMID 37724283

Authors

Dan-Qing Yu

Song-Ping Yu

Jing Wu

Li-Na Lan

Bang-Xun Mao

Affiliations

Soon will be listed here.

Abstract

Aim: To evaluate the effects of LIN28A (human) on high glucose-induced retinal pigmented epithelium (RPE) cell injury and its possible mechanism.

Methods: Diabetic retinopathy model was generated following 48h of exposure to 30 mmol/L high glucose (HG) in ARPE-19 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot tested the expression of the corresponding genes and proteins. Cell viability as well as apoptosis was determined through cell counting kit-8 (CCK-8) and flow cytometry assays. Immunofluorescence assay was adopted to evaluate autophagy activity. Caspase 3 activity, oxidative stress markers, and cytokines were appraised adopting their commercial kits, respectively. Finally, ARPE-19 cells were preincubated with EX527, a Sirtuin 1 (SIRT1) inhibitor, prior to HG stimulation to validate the regulatory mechanism.

Results: LIN28A was downregulated in HG-challenged ARPE-19 cells. LIN28A overexpression greatly inhibited HG-induced ARPE-19 cell viability loss, apoptosis, oxidative damage as well as inflammatory response. Meanwhile, the repressed autophagy and SIRT1 in ARPE-19 cells challenged with HG were elevated after LIN28A overexpression. In addition, treatment of EX527 greatly inhibited the activated autophagy following LIN28A overexpression and partly abolished the protective role of LIN28A against HG-elicited apoptosis, oxidative damage as well as inflammation in ARPE-19 cells.

Conclusion: LIN28A exerts a protective role against HG-elicited RPE oxidative damage, inflammation, as well as apoptosis regulating SIRT1/autophagy.

Citing Articles

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PMID: 39026915 PMC: 11246941. DOI: 10.18240/ijo.2024.07.04.

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