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http://dx.doi.org/10.5352/JLS.2009.19.10.1438

Inhibitory Effect of LPS-Induced Plasminogen Activator Inhibitor-1 by Ascofuranone in Rat Kidney Fibroblast Cells  

Chang, Young-Chae (Department of Pathology, Catholic University of Daegu School of Medicine)
Publication Information
Journal of Life Science / v.19, no.10, 2009 , pp. 1438-1443 More about this Journal
Abstract
Renal fibrosis is a final common manifestation of every type of chronic kidney disease. Plasminogen activator inhibitor (PAI)-1 is induced by lipopolysaccharide (LPS) and is known to play an essential role in the progress of renal fibrosis. In this paper, we found that an isoprenoid antibiotic, ascofuranone (AF), suppresses expression of profibrotic factors, PAI-1 and promoter activity of PAI-1 induced by LPS in rat kidney fibroblast cells. We therefore investigated signaling pathway mediated inhibitory effects of LPS-induced PAI-1 by AF in rNRK-49F cells. PAI-1 expression is suppressed by treatment with kinase inhibitors for MEK-1/2, as it isin inhibition of PAI-1 expression by AF, and AF inhibits phosphorylation of ERK-1/2. This study suggest that AF suppresses expression of PAI-1 through the inhibition of an ERK-1/2-dependent signal transduction pathway. The data indicates the possibility that AF can be used to prevent the development and progression of renal fibrosis.
Keywords
Renal fibrosis; fibronectin; ascofuranone; plasminogen activator inhibitor-1; renal Fibroblast;
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