Hypoxia induces the expression of membrane-type 1 matrix metalloproteinase in retinal glial cells

被引:27
作者
Noda, K
Ishida, S
Shinoda, H
Koto, T
Aoki, T
Tsubota, K
Oguchi, Y
Okada, Y
Ikeda, E
机构
[1] Keio Univ, Sch Med, Dept Pathol, Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Ophthalmol, Tokyo 1608582, Japan
[3] Daiichi Fine Chem Co Ltd, Toyama, Japan
关键词
D O I
10.1167/iovs.04-1528
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. Fibrovascular tissue formation in diabetic retinopathy necessitates not only angiogenic activity but also proteolytic activity, which is at least in part attributable to the induction of membrane-type 1 matrix metalloproteinase (MT1-MMP) in retinal glial cells. However, little is known about the triggers for MT1-MMP induction in the diabetic retina. In the present study, the effect of tissue hypoxia on MT1-MMP expression in retinal glial cells was investigated. METHODS. Retinal glial cells were isolated from the rabbit retina and cultured under either normoxic (20% O-2) or hypoxic (1% O-2) conditions in the presence or absence of the inhibitor for vascular endothelial growth factor ( VEGF) receptor signal transduction or a neutralizing antibody against VEGF. The expression level of MT1-MMP in retinal glial cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, Western blot analysis and immunocytochemistry. Expression of VEGF and VEGF receptors, VEGFR-1 and VEGFR-2, was also examined by RT-PCR. RESULTS. RT-PCR and real-time PCR analyses showed a 2.3-fold induction of MT1-MMP expression in retinal glial cells under hypoxic conditions. VEGF, especially its isoform VEGF 165, and VEGFR-2 were also upregulated in retinal glial cells by hypoxia, and hypoxia-induced MT1-MMP expression was inhibited in the presence of the VEGFR-2 inhibitor SU1498 or the anti-VEGF antibody. CONCLUSIONS. Hypoxia can induce MT1-MMP expression in retinal glial cells, and the hypoxia-induced expression of MT1-MMP is mediated by VEGF in an autocrine fashion.
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页码:3817 / 3824
页数:8
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