Fuchshofer, Rudolf and Yu, Alice L. and Teng, Hiang-Hwa and Strauss, Rupert and Kampik, Anselm and Welge-Lussen, Ulrich (2009) Hypoxia/reoxygenation induces CTGF and PAI-1 in cultured human retinal pigment epithelium cells. EXPERIMENTAL EYE RESEARCH, 88 (5). pp. 889-899. ISSN 0014-4835, 1096-0007
Full text not available from this repository. (Request a copy)Abstract
Early age-related macular degeneration (AMD) is characterized by thickening of Bruch's membrane due to the accumulation of extracellular matrix (ECM). This finding could be related to hypoxia of the retinal pigment epithelium (RPE). In the present study, we investigated the effects of hypoxia and reoxygenation on the expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1), collagen type IV (Col IV) and fibronectin (Fn) in cultured human RPE cells. Cultured human RPE cells were kept for 12-36 h under hypoxic conditions (1% O-2). Reoxygenation was conducted for 24 h. Hypoxia-mediated CTGF and PAI-1 expression were analyzed by using immunohistochemistry, Northern and Western blot analysis. Actinomycin D was added to examine whether hypoxia induces the transcription of CTGF and PAI-1 mRNA. Furthermore, cells were transfected with siRNA against hypoxia-inducible factor-1alpha (HIF-1 alpha) and kept under hypoxic conditions. The effects of antioxidants on hypoxia/reoxygenation-mediated CTGF and PAI-1 expression were tested by real-time PCR analysis. Production of Col IV and Fn were investigated by real-time PCR and Western blot analysis. Both hypoxia and hypoxia/reoxygenation increased the expression of CTGF, PAI-1, Col IV and Fn. Actinomycin D prevented the new transcription of CTGF and PAI-1 mRNA by hypoxia. Using siRNA against HIF-1 alpha, the hypoxia-mediated increase of CTGF and PAI-1 was inhibited. Antioxidants attenuated the reoxygenation-mediated increase of CTGF and PAI-1. The process of hypoxia/reoxygenation in the RPE may lead to an increase of ECM in the RPE and thus may contribute to the accumulation of ECM in Bruch's membrane. (C) 2008 Published by Elsevier Ltd.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLASMINOGEN-ACTIVATOR INHIBITOR-1; TISSUE GROWTH-FACTOR; HYPOXIA-RESPONSE ELEMENT; AGE-RELATED MACULOPATHY; INDUCIBLE FACTOR-I; MACULAR DEGENERATION; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; GENE-EXPRESSION; CHOROIDAL NEOVASCULARIZATION; hypoxia; reoxygenation; age-related macular degeneration; retinal pigment epithelium; extracellular matrix |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Sep 2020 10:17 |
| Last Modified: | 16 Sep 2020 10:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29039 |
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