Vascular endothelial growth factor expression by hyalocytes and its regulation by glucocorticoid

Y. Hata, Y. Sassa, T. Kita, M. Miura, K. Kano, S. Kawahara, R. Arita, S. Nakao, J. L. Shih, T. Ishibashi

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Abstract

Aim: Tumour necrosis factor-α (TNF-α) is one of the major inflammatory cytokines involved in the pathogenesis of various vitreoretinal diseases. The authors investigated the effect of hypoxia, TNF-α and dexamethasone on vascular endothelial growth factor (VEGF) expression by cultured hyalocytes. Methods: Hyalocytes were isolated from bovine vitreous. Hypoxie and TNF-α-dependent effects on cultured hyalocytes were investigated using several assays to determine VEGF protein expression, hypoxia-inducible factor (HIF)-1α protein levels, HIF-1α-DNA-binding ability and VEGF mRNA stability. The effects of dexamethasone on VEGF expression and its intracellular signalling under hypoxic or TNF-α stimulated conditions were also examined. Results: Hypoxic conditions and TNF-α stimulation induce VEGF expression in hyalocytes. These stimuli also stabilise HIF-1α protein and increase its DNA-binding ability. Dexamethasone significantly inhibits both HIF-1α protein levels and HIF-1α-DNA-binding activity, and also decreases the hypoxic- and TNF-α -dependent induction of VEGF expression in hyalocyte. However, dexamethasone has no significant effect on the stability of VEGF mRNA. Conclusions: Hyalocytes may be involved in various vitreoretinal diseases by increasing HIF-1α protein stability and HIF-1α-DNA binding, and thus increasing VEGF production under pathological conditions. Dexamethasone seems to be capable of inhibiting hypoxic and TNF-α dependent VEGF production, presumably via its inhibitory effects on HIF-1α protein levels and its DNA-binding activity.

Original languageEnglish
Pages (from-to)1540-1544
Number of pages5
JournalBritish Journal of Ophthalmology
Volume92
Issue number11
DOIs
Publication statusPublished - Nov 1 2008

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All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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