Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Fuchshofer, R; Yu, AL; Teng, HH; Strauss, R; Kampik, A; Welge-Lussen, U.
Hypoxia/reoxygenation induces CTGF and PAI-1 in cultured human retinal pigment epithelium cells.
Exp Eye Res. 2009; 88(5):889-899 Doi: 10.1016/j.exer.2008.11.036
Web of Science PubMed FullText FullText_MUG

Co-authors Med Uni Graz: Strauß Rupert
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
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 12-36h under hypoxic conditions (1% O(2)). Reoxygenation was conducted for 24h. 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-1alpha) 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-1alpha, 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.
Find related publications in this database (using NLM MeSH Indexing): Adolescent -; Adult -; Aged -; Antioxidants - pharmacology; Cell Hypoxia - physiology; Cells, Cultured -; Collagen Type IV - biosynthesis Collagen Type IV - genetics; Connective Tissue Growth Factor - biosynthesis Connective Tissue Growth Factor - genetics; Fibronectins - biosynthesis Fibronectins - genetics; Gene Expression Regulation -; Humans -; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Macular Degeneration - metabolism Macular Degeneration - pathology; Middle Aged -; Oxygen - pharmacology; Plasminogen Activator Inhibitor 1 - biosynthesis Plasminogen Activator Inhibitor 1 - genetics; RNA Interference -; RNA, Messenger - genetics; RNA, Small Interfering - genetics; Retinal Pigment Epithelium - cytology Retinal Pigment Epithelium - metabolism; Transcriptional Activation -; Transfection -; Young Adult -
Find related publications in this database (Keywords): hypoxia; reoxygenation; age-related macular degeneration; retinal pigment epithelium; extracellular matrix