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 language | English |
|---|---|
| Pages (from-to) | 1540-1544 |
| Number of pages | 5 |
| Journal | British Journal of Ophthalmology |
| Volume | 92 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2008 |
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All Science Journal Classification (ASJC) codes
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
Cite this
Vascular endothelial growth factor expression by hyalocytes and its regulation by glucocorticoid. / Hata, Y.; Sassa, Y.; Kita, T.; Miura, M.; Kano, K.; Kawahara, S.; Arita, R.; nakao, shintaro; Shih, J. L.; Ishibashi, Tatsuro.
In: British Journal of Ophthalmology, Vol. 92, No. 11, 01.11.2008, p. 1540-1544.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vascular endothelial growth factor expression by hyalocytes and its regulation by glucocorticoid
AU - Hata, Y.
AU - Sassa, Y.
AU - Kita, T.
AU - Miura, M.
AU - Kano, K.
AU - Kawahara, S.
AU - Arita, R.
AU - nakao, shintaro
AU - Shih, J. L.
AU - Ishibashi, Tatsuro
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=55449100169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55449100169&partnerID=8YFLogxK
U2 - 10.1136/bjo.2008.141002
DO - 10.1136/bjo.2008.141002
M3 - Article
C2 - 18952656
AN - SCOPUS:55449100169
VL - 92
SP - 1540
EP - 1544
JO - British Journal of Ophthalmology
JF - British Journal of Ophthalmology
SN - 0007-1161
IS - 11
ER -