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Y. Terasaka, D. Miyazaki, K. Yakura, Y. Inoue; Transcriptional Profiling of Herpes Simplex Virus-Infected-Human Corneal Epithelium. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4628.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize transcriptional responses of corneal epithelial cells after herpes simplex virus (HSV) infection and identify crucial signaling events via approaches utilizing network analysis.
Immortalized human corneal epithelial cells were infected with HSV-1 strain KOS. The transcriptional responses of 30000 genes were analyzed using whole human genome chip(Agilent). Molecular networks of HSV-induced genes were constructed using GeneSpring GX7.3.1 and Ingenuity Pathway Analysis(IPA) . Representative network cascade was verified using real time-RT-PCR and ELISA.
ANOVA analysis of HSV-induced-transcriptome identified 412 genes (P<0.05, 2< or 0.5> threshold). The gene set was used to probe HSV-responsive signal transduction pathways. Pathway analysis using Kyoto Encyclopedia of Genes and Genomes identified MAP kinase signaling, cytokine-cytokine receptor interaction, focal adhesion, and carcinogenesis. Network analysis predicted IL-6 and VEGF as crucial nodes of signaling events (significance score 19).HSV-stimulated-cytokine analysis by ELISA kinetically verified their induction. Neutralization of IL-6 significantly suppressed HSV-induced-VEGF secretion.
Comprehensive transcriptional analysis identified IL-6 and VEGF as presumable key modulators in HSV infected corneal epithelium. Since VEGF has been already recognized as an important player in stromal herpetic keratitis, up-regulation of VEGF in HSV corneal epithelial infection suggests very early participation of VEGF in the pathogenesis of herpetic keratitis.
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