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Vascular endothelial growth factor expression by hyalocytes and its regulation by glucocorticoid
  1. Y Hata1,
  2. Y Sassa1,
  3. T Kita1,
  4. M Miura1,
  5. K Kano1,
  6. S Kawahara1,
  7. R Arita1,
  8. S Nakao1,
  9. J L Shih2,
  10. T Ishibashi1
  1. 1
    Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
  2. 2
    Research Division, Joslin Diabetes Center, Boston, Massachusetts, USA
  1. Dr Y Hata, Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan; hatachan{at}med.kyushu-u.ac.jp

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. Hypoxic 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.

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Footnotes

  • Funding: The study was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japan (Grant-in-Aid for Scientific Research #19592026).

  • Competing interests: None.

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