Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy

BackgroundDiabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which is associated with damage of blood-retinal barrier and ischemia of retinal vasculature. It devastates visual acuity due to leakage of retinal vessels and aberrant pathological angiogenesis in...

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Main Authors: Nan Wang, Linfeng Wei, Die Liu, Quyan Zhang, Xiaobo Xia, Lexi Ding, Siqi Xiong
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.867600/full
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author Nan Wang
Nan Wang
Linfeng Wei
Die Liu
Die Liu
Quyan Zhang
Quyan Zhang
Xiaobo Xia
Xiaobo Xia
Lexi Ding
Lexi Ding
Siqi Xiong
Siqi Xiong
author_facet Nan Wang
Nan Wang
Linfeng Wei
Die Liu
Die Liu
Quyan Zhang
Quyan Zhang
Xiaobo Xia
Xiaobo Xia
Lexi Ding
Lexi Ding
Siqi Xiong
Siqi Xiong
author_sort Nan Wang
collection DOAJ
description BackgroundDiabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which is associated with damage of blood-retinal barrier and ischemia of retinal vasculature. It devastates visual acuity due to leakage of retinal vessels and aberrant pathological angiogenesis in diabetic patients. The etiology of DR is complex, accumulated studies have shown that autophagy plays an important role in the pathogenesis of DR, but its specific mechanism needs to be further studied.MethodsThis study chose the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE146615 to carry on the research. Autophagy-related genes that were potentially differentially expressed in DR were screened by R software. Then, the differentially expressed autophagy-related genes were analyzed by correlation analysis, tissue-specific gene expression, gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) network analysis. Finally, retinal pigment epithelial cell line (ARPE-19) incubated with high glucose (HG) was used to mimic the DR model, and the mRNA level of key genes was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in vitro.ResultsA total of 23 differentially expressed autophagy-related genes (9 up-regulated genes and 14 down-regulated genes) were identified by differential expression analysis. The analysis of tissue-specific gene expression showed that these differentially expressed autophagy-related genes were enriched in the retina. GO and KEGG enrichment analysis showed that differentially expressed autophagy-related genes were significantly enriched in autophagy-related pathways such as regulation of autophagy and macroautophagy. Then 10 hub genes were identified by PPI network analysis and construction of key modules. Finally, qRT-PCR confirmed that the expression of MAPK3 in the DR model was consistent with the results of bioinformatics analysis of mRNA chip.ConclusionThrough bioinformatics analysis, we identified 23 potential DR autophagy-related genes, among which the down-regulated expression of MAPK3 may affect the occurrence and development of DR by regulating autophagy. It provides a novel insight into the pathogenesis of DR.
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spelling doaj.art-9fec7cdec9284c598c14c01379563cea2022-12-22T02:56:04ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-04-011310.3389/fendo.2022.867600867600Identification and Validation of Autophagy-Related Genes in Diabetic RetinopathyNan Wang0Nan Wang1Linfeng Wei2Die Liu3Die Liu4Quyan Zhang5Quyan Zhang6Xiaobo Xia7Xiaobo Xia8Lexi Ding9Lexi Ding10Siqi Xiong11Siqi Xiong12Eye Center of Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Opthalmology, Central South University, Changsha, ChinaDepartment of General Surgery, Zhongshan Hospital of Dalian University, Dalian, ChinaEye Center of Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Opthalmology, Central South University, Changsha, ChinaEye Center of Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Opthalmology, Central South University, Changsha, ChinaEye Center of Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Opthalmology, Central South University, Changsha, ChinaEye Center of Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Opthalmology, Central South University, Changsha, ChinaEye Center of Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Opthalmology, Central South University, Changsha, ChinaBackgroundDiabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which is associated with damage of blood-retinal barrier and ischemia of retinal vasculature. It devastates visual acuity due to leakage of retinal vessels and aberrant pathological angiogenesis in diabetic patients. The etiology of DR is complex, accumulated studies have shown that autophagy plays an important role in the pathogenesis of DR, but its specific mechanism needs to be further studied.MethodsThis study chose the online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE146615 to carry on the research. Autophagy-related genes that were potentially differentially expressed in DR were screened by R software. Then, the differentially expressed autophagy-related genes were analyzed by correlation analysis, tissue-specific gene expression, gene-ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) network analysis. Finally, retinal pigment epithelial cell line (ARPE-19) incubated with high glucose (HG) was used to mimic the DR model, and the mRNA level of key genes was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in vitro.ResultsA total of 23 differentially expressed autophagy-related genes (9 up-regulated genes and 14 down-regulated genes) were identified by differential expression analysis. The analysis of tissue-specific gene expression showed that these differentially expressed autophagy-related genes were enriched in the retina. GO and KEGG enrichment analysis showed that differentially expressed autophagy-related genes were significantly enriched in autophagy-related pathways such as regulation of autophagy and macroautophagy. Then 10 hub genes were identified by PPI network analysis and construction of key modules. Finally, qRT-PCR confirmed that the expression of MAPK3 in the DR model was consistent with the results of bioinformatics analysis of mRNA chip.ConclusionThrough bioinformatics analysis, we identified 23 potential DR autophagy-related genes, among which the down-regulated expression of MAPK3 may affect the occurrence and development of DR by regulating autophagy. It provides a novel insight into the pathogenesis of DR.https://www.frontiersin.org/articles/10.3389/fendo.2022.867600/fulldiabetic retinopathyautophagydifferentially expressed genesprotein-protein interaction networkMAPK3
spellingShingle Nan Wang
Nan Wang
Linfeng Wei
Die Liu
Die Liu
Quyan Zhang
Quyan Zhang
Xiaobo Xia
Xiaobo Xia
Lexi Ding
Lexi Ding
Siqi Xiong
Siqi Xiong
Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy
Frontiers in Endocrinology
diabetic retinopathy
autophagy
differentially expressed genes
protein-protein interaction network
MAPK3
title Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy
title_full Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy
title_fullStr Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy
title_full_unstemmed Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy
title_short Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy
title_sort identification and validation of autophagy related genes in diabetic retinopathy
topic diabetic retinopathy
autophagy
differentially expressed genes
protein-protein interaction network
MAPK3
url https://www.frontiersin.org/articles/10.3389/fendo.2022.867600/full
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