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2003 | 50 | 3 | 677-689

Article title

Prostaglandin-J2 upregulates expression of matrix metalloproteinase-1 independently of activation of peroxisome proliferator-activated receptor-γ.

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EN

Abstracts

EN
Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-inducible nuclear receptor that functions as a transcription factor involved in lipid metabolism, inflammatory response and angiogenesis. The most potent endogenous PPARγ activator is 15-deoxy-Δ12,14prostaglandin-J2 (15d-PGJ2), whereas synthetic ligands include the oral antidiabetic drugs thiazolidinediones (TZDs). Activation of PPARγ was reported to decrease the synthesis of matrix metalloproteinases (MMPs) in vascular smooth muscle cells and macrophages. We aimed to investigate the effect of PPARγ ligands on expression of MMP-1 and urokinase plasminogen activator (uPA) in human microvascular endothelial cells (HMEC-1). We found that treatment of HMEC-1 with 15d-PGJ2 increased the synthesis of MMP-1 protein up to 168% comparing to untreated cells. TZDs (ciglitazone and troglitazone), more potent activators of PPARγ in HMEC-1, did not influence MMP-1 production, arguing against the involvement of PPARγ in this process. Importantly, the stimulatory effect of 15d-PGJ2 was reversed by the antioxidant N-acetyl-cysteine (NAC), suggesting a contribution of oxidative stress. We demonstrated also that 15d-PGJ2 did not change the activity of MMP-1 promoter, but increased the stability of MMP-1 mRNA. In contrast, 15d-PGJ2 very potently inhibited the synthesis of uPA. This effect was in part mimicked by ciglitazone and troglitazone implying an involvement of PPARγ. Accordingly, NAC did not modify the inhibitory effect of 15d-PGJ2 on uPA expression. In conclusion, we postulate that 15d-PGJ2 may differently regulate the synthesis of proteases involved in angiogenesis : it upregulates MMP-1 expression in HMEC-1 through induction of oxidative stress, and inhibits uPA synthesis partly by activation of PPARγ.

Year

Volume

50

Issue

3

Pages

677-689

Physical description

Dates

published
2003
received
2003-05-30
revised
2003-08-12
accepted
2003-09-05

Contributors

  • Department of Molecular Genetics, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland
author
  • Department of Vascular Surgery, University of Vienna, Vienna, Austria
  • Department of Cardiothoracic Surgery, University of Vienna, Vienna, Austria
  • Department of Cell Biochemistry, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland
  • Department of Cardiothoracic Surgery, University of Vienna, Vienna, Austria
author
  • Department of Cell Biochemistry, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland

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bwmeta1.element.bwnjournal-article-abpv50i3p677kz
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