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2003 | 50 | 3 |

Tytuł artykułu

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

Warianty tytułu

Języki publikacji

EN

Abstrakty

EN
Peroxisome proliferator-activated receptor-y (PPARy) 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-Δ12,14,prostaglandin-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 PPARy 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 PPAR in HMEC-1, did not influence MMP-1 production, arguing against the involvement of PPAR 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 PPAR. 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.

Wydawca

-

Rocznik

Tom

50

Numer

3

Opis fizyczny

p.677-689,fig.

Twórcy

autor
  • Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland
autor
autor
autor
autor
autor

Bibliografia

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Bibliografia

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