Identification of pathogenic genes and upstream regulators in age-related macular degenerationReportar como inadecuado

Identification of pathogenic genes and upstream regulators in age-related macular degeneration - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Ophthalmology

, 17:102



BackgroundAge-related macular degeneration AMD is the leading cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AMD.

MethodsTo screen pathogenic genes of AMD, an integrated analysis was performed by using the microarray datasets in AMD derived from the Gene Expression Omnibus GEO database. The functional annotation and potential pathways of differentially expressed genes DEGs were further discovered by Gene Ontology GO and Kyoto Encyclopedia of Genes and Genomes KEGG enrichment analysis. We constructed the AMD-specific transcriptional regulatory network to find the crucial transcriptional factors TFs which target the DEGs in AMD. Quantitative real time polymerase chain reaction qRT-PCR was performed to verify the DEGs and TFs obtained by integrated analysis.

ResultsFrom two GEO datasets obtained, we identified 1280 DEGs 730 up-regulated and 550 down-regulated genes between AMD and normal control NC. After KEGG analysis, steroid biosynthesis is a significantly enriched pathway for DEGs. The expression of 8 genes TNC, GRP, TRAF6, ADAMTS5, GPX3, FAP, DHCR7 and FDFT1 was detected. Except for TNC and GPX3, the other 6 genes in qRT-PCR played the same pattern with that in our integrated analysis.

ConclusionsThe dysregulation of these eight genes may involve with the process of AMD. Two crucial transcription factors c-rel and myogenin were concluded to play a role in AMD. Especially, myogenin was associated with AMD by regulating TNC, GRP and FAP. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AMD.

KeywordsAge-related macular degeneration Transcription factors  Differentially expressed genes Integrated analysis AbbreviationsADAMTS5ADAM metallopeptidase with thrombospondin type 1 motif 5

AMDAge-related macular degeneration

CNVchoroidal neovascularization

DEGsdifferentially expressed genes

DHCR77-dehydrocholesterol reductase

FAPfibroblast activation protein alpha

FDFTfarnesyl-diphosphate farnesyl transferase 1.

GEOGene Expression Omnibus database

GOGene Ontology

GPX3glutathione peroxidase 3

GRPgastrin-releasing peptide

KEGGKyoto Encyclopedia of Genes and Genomes

MEmacular eduma

RPEretinal pigment epithelium

TFstranscription factors


TRAF6TNF receptor associated factor 6

VEGFvascular endothelial growth factor

Electronic supplementary materialThe online version of this article doi:10.1186-s12886-017-0498-z contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Bin Zhao - Mengya Wang - Jing Xu - Min Li - Yuhui Yu


Documentos relacionados