Up regulation of VEGF gene expression by PGE2 stimulation in cultured rat muller cells

T. Cheng, R. Wen, W. Cao, R. H. Steinberg

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Purpose. Neovascular disease of the retina is a major cause of blindness. Vascular endothelial growth factor (VEGF) is a potent, specific mitogen for vascular endothelial cells and promotes neovascularization in vivo. PGE2 is a pathogenetic mediator in the central nervous system and has been recently reported inducing VEGF expression in osteoblasts. To determine whether PGE2 induces VEGF gene expression in Müller cells, we performed Northern blot analysis and found that PGE2 up-regulated VEGF expression in cultured rat Müller cells, and this occurs through activation of protein kinase C (PKC). Methods. Müller cells from 1-3 day Sprague-Dawley rats were isolated and cultured with Eagle MEM+10% FCS. Cells at passage1-4 were treated with PGE2, PKC inhibitor H-7, adenylate cyclase inhibitor SQ22536. Northern blot analysis was performed to determine VEGF mRNA levels. Results. Cells were identified by immunocytochemistry with antibodies against Müller cell markers: vimentin, carbonic anhydrase C, and glutamine synthetase. The PGE2-induced up-regulation of VEGF mRNA increased by 1.5, 1.8, 2.0, and 2.5-fold at concentrations of 0.1, 1.0, 10, and 100 μM respectively. The time course of induction revealed a 1.7-fold increase in VEGF mRNA 1 hr after PGE2 treatment, which reached 2.3-fold by 2 hr, then declined to 1.8-fold by 4 br. The PGE2-induced up-regulation of VEGF mRNA was completely blocked by the PKC inhibitor H-7, while not by the adenylate cyclase inhibitor SQ22536. Conclusions: Our results indicate that PGE2 induces VEGF expression in cultured Müller cells and the induction seems to be through PKC activation. These findings raise the possibility that PGE2 may be involved in neovascular disease of the retina by simulating Müller cell VEGF expression.

Original languageEnglish (US)
Pages (from-to)S793
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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