Vascular endothelial growth factor expression by hyalocytes and its regulation by glucocorticoid. Issue 11 (24th October 2008)

• Record Type: Journal Article
• Authors: Hata, Y; Sassa, Y; Kita, T; Miura, M; Kano, K; Kawahara, S; Arita, R; Nakao, S; Shih, J L; Ishibashi, T
• Is Part Of: British journal of ophthalmology. Volume 92:Issue 11(2008)
• Page Start: 1540
• Page End: 1544
• Publication Date: 2008-10-24
• Subjects: Ophthalmology -- Periodicals; 617.7
• DOI: 10.1136/bjo.2008.141002
• Languages: English
• ISSNs: 0007-1161

Abstract

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.