MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4

Diabetic retinopathy (DR) is a type of diabetes complication, which can result in loss of vision in adults worldwide. Increasing evidence has revealed that microRNAs (miRs) can regulate DR progression. Thus, the present study was aimed at assessing the possible mechanism of miR-139-5p in high glucos...

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Main Authors: Kan Shao, Gong Chen, Lili Xia, Cheng Chen, Shan Huang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/1629783
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author Kan Shao
Gong Chen
Lili Xia
Cheng Chen
Shan Huang
author_facet Kan Shao
Gong Chen
Lili Xia
Cheng Chen
Shan Huang
author_sort Kan Shao
collection DOAJ
description Diabetic retinopathy (DR) is a type of diabetes complication, which can result in loss of vision in adults worldwide. Increasing evidence has revealed that microRNAs (miRs) can regulate DR progression. Thus, the present study was aimed at assessing the possible mechanism of miR-139-5p in high glucose- (HG-) incubated retinal pigment epithelial (ARPE-19) cells. The present results demonstrated that miR-139-5p expression was notably reduced in the serum samples of patients with DR, as well as in ARPE-19 cells treated with HG in a time-dependent manner. Moreover, miR-139-5p was markedly overexpressed by transfection of miR-139-5p mimics into ARPE-19 cells. Overexpression of miR-139-5p markedly induced cell viability and repressed HG-triggered apoptosis. Furthermore, overexpression of miR-139-5p relived HG-enhanced oxidative stress injury. It was found that HG induced malondialdehyde levels but decreased superoxide dismutase and glutathione peroxidase activities in ARPE-19 cells. In addition, overexpression of miR-139-5p could markedly decrease intracellular stress. The results demonstrated that overexpression of miR-139-5p effectively repressed HG-activated inflammation, as indicated by the upregulation of inflammation cytokines, including TNF-α, IL-6, and Cox-2, in ARPE-19 cells. Subsequently, it was identified that LIM-only factor 4 (LMO4) could act as a downstream target for miR-139-5p. LMO4 expression was significantly increased in patients with DR and HG-treated ARPE-19 cells. Mechanistically, knockdown of LMO4 reversed the biological role of miR-139-5p in proliferation, apoptosis, oxidative stress, and release of inflammation factors in vitro. Collectively, these results suggested that miR-139-5p significantly decreased ARPE-19 cell injury caused by HG by inducing proliferation and suppressing cell apoptosis, oxidant stress, and inflammation by modulating LMO4.
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spelling doaj-art-7793838c53ed4cbf97051c284a9b8aab2025-08-20T03:35:38ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/16297831629783MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4Kan Shao0Gong Chen1Lili Xia2Cheng Chen3Shan Huang4Department of Endocrinology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSchool of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai, ChinaDepartment of Endocrinology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSchool of Environmental and Materials Engineering, College of Engineering, Shanghai Polytechnic University, Shanghai, ChinaDepartment of Endocrinology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDiabetic retinopathy (DR) is a type of diabetes complication, which can result in loss of vision in adults worldwide. Increasing evidence has revealed that microRNAs (miRs) can regulate DR progression. Thus, the present study was aimed at assessing the possible mechanism of miR-139-5p in high glucose- (HG-) incubated retinal pigment epithelial (ARPE-19) cells. The present results demonstrated that miR-139-5p expression was notably reduced in the serum samples of patients with DR, as well as in ARPE-19 cells treated with HG in a time-dependent manner. Moreover, miR-139-5p was markedly overexpressed by transfection of miR-139-5p mimics into ARPE-19 cells. Overexpression of miR-139-5p markedly induced cell viability and repressed HG-triggered apoptosis. Furthermore, overexpression of miR-139-5p relived HG-enhanced oxidative stress injury. It was found that HG induced malondialdehyde levels but decreased superoxide dismutase and glutathione peroxidase activities in ARPE-19 cells. In addition, overexpression of miR-139-5p could markedly decrease intracellular stress. The results demonstrated that overexpression of miR-139-5p effectively repressed HG-activated inflammation, as indicated by the upregulation of inflammation cytokines, including TNF-α, IL-6, and Cox-2, in ARPE-19 cells. Subsequently, it was identified that LIM-only factor 4 (LMO4) could act as a downstream target for miR-139-5p. LMO4 expression was significantly increased in patients with DR and HG-treated ARPE-19 cells. Mechanistically, knockdown of LMO4 reversed the biological role of miR-139-5p in proliferation, apoptosis, oxidative stress, and release of inflammation factors in vitro. Collectively, these results suggested that miR-139-5p significantly decreased ARPE-19 cell injury caused by HG by inducing proliferation and suppressing cell apoptosis, oxidant stress, and inflammation by modulating LMO4.http://dx.doi.org/10.1155/2021/1629783
spellingShingle Kan Shao
Gong Chen
Lili Xia
Cheng Chen
Shan Huang
MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4
Mediators of Inflammation
title MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4
title_full MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4
title_fullStr MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4
title_full_unstemmed MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4
title_short MicroRNA-139-5p Alleviates High Glucose-Triggered Human Retinal Pigment Epithelial Cell Injury by Targeting LIM-Only Factor 4
title_sort microrna 139 5p alleviates high glucose triggered human retinal pigment epithelial cell injury by targeting lim only factor 4
url http://dx.doi.org/10.1155/2021/1629783
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