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

Br J Ophthalmol. 2008 Nov;92(11):1540-4. doi: 10.1136/bjo.2008.141002.

Abstract

Aim: Tumour necrosis factor-alpha (TNF-alpha) is one of the major inflammatory cytokines involved in the pathogenesis of various vitreoretinal diseases. The authors investigated the effect of hypoxia, TNF-alpha and dexamethasone on vascular endothelial growth factor (VEGF) expression by cultured hyalocytes.

Methods: Hyalocytes were isolated from bovine vitreous. Hypoxic and TNF-alpha-dependent effects on cultured hyalocytes were investigated using several assays to determine VEGF protein expression, hypoxia-inducible factor (HIF)-1alpha protein levels, HIF-1alpha-DNA-binding ability and VEGF mRNA stability. The effects of dexamethasone on VEGF expression and its intracellular signalling under hypoxic or TNF-alpha stimulated conditions were also examined.

Results: Hypoxic conditions and TNF-alpha stimulation induce VEGF expression in hyalocytes. These stimuli also stabilise HIF-1alpha protein and increase its DNA-binding ability. Dexamethasone significantly inhibits both HIF-1alpha protein levels and HIF-1alpha-DNA-binding activity, and also decreases the hypoxic- and TNF-alpha -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-1alpha protein stability and HIF-1alpha-DNA binding, and thus increasing VEGF production under pathological conditions. Dexamethasone seems to be capable of inhibiting hypoxic and TNF-alpha dependent VEGF production, presumably via its inhibitory effects on HIF-1alpha protein levels and its DNA-binding activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Hypoxia / drug effects*
  • Cell Hypoxia / physiology
  • DNA / metabolism
  • Dexamethasone / pharmacology
  • Glucocorticoids / pharmacology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Vascular Endothelial Growth Factor A / drug effects
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor A / physiology
  • Vitreous Body / cytology*

Substances

  • Glucocorticoids
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Dexamethasone
  • DNA