A systems genetics approach to revealing the Pdgfb molecular network of the retina.
Mol Vis
; 26: 459-471, 2020.
Article
en En
| MEDLINE
| ID: mdl-32587457
ABSTRACT
Purpose:
Platelet-derived growth factor (PDGF) signaling is well known to be involved in vascular retinopathies. Among the PDGF family, the subunit B (PDGFB) protein is considered a promising therapeutic target. This study aimed to identify the genes and potential pathways through which PDGFB affects retinal phenotypes by using a systems genetics approach.Methods:
Gene expression data had been previously generated in a laboratory for the retinas of 75 C57BL/6J(B6) X DBA/2J (BXD) recombinant inbred (RI) strains. Using this data, the genetic correlation method was used to identify genes correlated to Pdgfb. A correlation between intraocular pressure (IOP) and Pdgfb was calculated based on the Pearson correlation coefficient. A gene set enrichment analysis and the STRING database were used to evaluate gene function and to construct protein-protein interaction (PPI) networks.Results:
Pdgfb was a cis-regulated gene in the retina; its expression had a significant correlation with IOP (r = 0.305; p value = 0.012). The expression levels of 2,477 genes also had significant correlations with Pdgfb expressions (p<0.05), among which Atf4 was the most positively correlated (r = 0.628; p value = 1.29e-10). Thus, Atf4 was highly expressed in the retina and shared the transcription factor (TF) Hnf4a binding site with Pdgfb. Gene Ontology and a pathway analysis revealed that Pdgfb and its covariates were highly involved in mitogen-activated protein kinase (MAPK) and vascular endothelial growth factor (VEGF) pathways. A generated gene network indicated that Pdgfb was directly connected to and interacted with other genes with similar biologic functions.Conclusions:
A systems genetics analysis revealed that Pdgfb had significant interactions with Atf4 and other genes in MAPK and VEGF pathways, through which Pdgfb was important in maintaining retina function. These findings provided basic information regarding the Pdgfb regulation mechanism and potential therapy for vascular retinopathies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Retina
/
Factor de Crecimiento Derivado de Plaquetas
/
Linfocinas
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Sistema de Señalización de MAP Quinasas
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Factor A de Crecimiento Endotelial Vascular
/
Biología de Sistemas
/
Factor de Transcripción Activador 4
/
Redes Reguladoras de Genes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Vis
Asunto de la revista:
BIOLOGIA MOLECULAR
/
OFTALMOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China