Identification of pathogenic genes and upstream regulators in age-related macular degeneration

Zhao, Bin; Wang, Mengya; Xu, Jing; Li, Min; Yu, Yuhui

doi:10.1186/s12886-017-0498-z

Cited by 20 publications

(20 citation statements)

References 31 publications

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“…FDFT1 has been reported to be related to sterol synthesis, which is expected to increase intracellular cholesterol and is associated with type 2 diabetes and coronary artery calcium [43]. FDFT1 has been found to be enriched in steroid biosynthesis pathway and upregulated in AMD by Zhao et al [44]. They infer that FDFT1 may induce AMD by elevating the expression of cholesterol, which coincides with our results.…”

Section: Discussionsupporting

confidence: 91%

Bioinformatical Analysis of miRNA‐mRNA Interaction Network Underlying Macrophage Aging and Cholesterol‐Responsive Difference between Young and Aged Macrophages

Yin

Zhang

et al. 2020

BioMed Research International

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Purpose. Macrophage aging is involved with the occurrence and progression of age-related macular degeneration (AMD). The purpose of this study was to identify the specific microRNAs (miRNA), mRNAs, and their interactions underlying macrophage aging and response to cholesterol through bioinformatical analysis in order to get a better understanding of the mechanism of AMD. Methods. The microarray data were obtained from Gene Expression Omnibus (accession GSE111304 and GSE111382). The age-related differentially expressed genes in macrophages were identified using R software. Further miRNA-mRNA interactions were analyzed through miRWalk, mirTarBase, starBase, and then produced by Cytoscape. The functional annotations including Gene Ontology and KEGG pathways of the miRNA target genes were performed by the DAVID and the STRING database. In addition, protein-protein interaction network was constructed to identify the key genes in response to exogenous cholesterol. Results. When comparing aged and young macrophages, a total of 14 miRNAs and 101 mRNAs were detected as differentially expressed. Besides, 19 validated and 544 predicted miRNA-mRNA interactions were detected. Lipid metabolic process was found to be associated with macrophage aging through functional annotations of the miRNA targets. After being treated with oxidized and acetylated low-density lipoprotein, miR-714 and 16 mRNAs differentially expressed in response to both kinds of cholesterol between aged and young macrophages. Among them, 6 miRNA-mRNA predicted pairs were detected. The functional annotations were mainly related to lipid metabolism process and farnesyl diphosphate farnesyl transferase 1 (FDFT1) was identified to be the key gene in the difference of response to cholesterol between aged and young macrophages. Conclusions. Lipid metabolic process was critical in both macrophage aging and response to cholesterol thus was regarded to be associated with the occurrence and progression of AMD. Moreover, miR-714-FDFT1 may modulate cholesterol homeostasis in aged macrophages and have the potential to be a novel therapeutic target for AMD.

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Section: Discussionsupporting

confidence: 91%

Bioinformatical Analysis of miRNA‐mRNA Interaction Network Underlying Macrophage Aging and Cholesterol‐Responsive Difference between Young and Aged Macrophages

Yin

Zhang

et al. 2020

BioMed Research International

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“…Several biological pathways have been implicated in the pathogenesis of age-related macular degeneration 32 . These include senescence, shown by lipofuscin accumulation in retinal pigment epithelium cells, choroidal ischaemia, and oxidative damage 33 .…”

Section: Discussionmentioning

confidence: 99%

Advanced glycation end products promote VEGF expression and thus choroidal neovascularization via Cyr61-PI3K/AKT signaling pathway

Sun

Huang

et al. 2017

Sci Rep

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Choroidal neovascularisation (CNV) causes severe vision loss among old patients, especially those with diabetes. Previously, Cyr61 has been found to play a critical role in the pathogenesis of both AMD and diabetes. In the present study, we found that increased CNV severity together with higher expression of Cyr61 and VEGF in diabetes mice compared with control mice. Moreover, knockdown of Cyr61 decreased CNV severity. In vitro mechanism study revealed that the advanced glycation end products (AGEs) significantly increased the expression of Cyr61 in retinal pigment epithelial (RPE) cells, mimicking the effects of diabetes. In turn, the increased Cyr61 enhanced VEGF expression through FAK and PI3K/Akt pathways. Chemically blocking the above pathway significantly inhibited CNV formation, providing a new strategy for clinical prevention and treatment of CNV in related diseases.

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“…Due to differences of samples and platforms in multiple microarray studies, integrated analysis of multiple microarray studies can identify more accurate profiles of DEGs with a larger sample size than a single microarray. Exploring the upstream transcription factors (TFs) mediating abnormal gene expression in disease status can help to understand pathophysiological changes in complex diseases (Li, Dani, & Le, ; Zhao, Wang, Xu, Li, & Yu, ).…”

Section: Introductionmentioning

confidence: 99%

Identification of key genes and upstream regulators in ischemic stroke

Zhang

Chen

et al. 2019

Brain and Behavior

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Introduction Ischemic stroke (IS) causes severe neurological impairments and physical disabilities and has a high economic burden. Our study aims to identify the key genes and upstream regulators in IS by integrated microarray analysis. Methods An integrated analysis of microarray studies of IS was performed to identify the differentially expressed genes (DEGs) in IS compared to normal control. Based on these DEGs, we performed the functional annotation and transcriptional regulatory network constructions. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to verify the expression of DEGs. Results From two Gene Expression Omnibus datasets obtained, we obtained 1526 DEGs (534 up‐regulated and 992 down‐regulated genes) between IS and normal control. The results of functional annotation showed that Oxidative phosphorylation and Alzheimer's disease were significantly enriched pathways in IS. Top four transcription factors (TFs) with the most downstream genes including PAX4, POU2F1, ELK1, and NKX2‐5. The expression of six genes (ID3, ICAM2, DCTPP1, ANTXR2, DUSP1, and RGS2) was detected by qRT‐PCR. Except for DUSP1 and RGS2, the other four genes in qRT‐PCR played the same pattern with that in our integrated analysis. Conclusions The dysregulation of these six genes may involve with the process of ischemic stroke (IS). Four TFs (PAX4, POU2F1, ELK1 and NKX2‐5) were concluded to play a role in IS. Our finding provided clues for exploring mechanism and developing novel diagnostic and therapeutic strategies for IS.

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Identification of pathogenic genes and upstream regulators in age-related macular degeneration

Cited by 20 publications

References 31 publications

Bioinformatical Analysis of miRNA‐mRNA Interaction Network Underlying Macrophage Aging and Cholesterol‐Responsive Difference between Young and Aged Macrophages

Bioinformatical Analysis of miRNA‐mRNA Interaction Network Underlying Macrophage Aging and Cholesterol‐Responsive Difference between Young and Aged Macrophages

Advanced glycation end products promote VEGF expression and thus choroidal neovascularization via Cyr61-PI3K/AKT signaling pathway

Identification of key genes and upstream regulators in ischemic stroke

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