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- W2003203559 abstract "Fibrosis in glomerulosclerosis causes progressive loss of renal function. Transforming growth factor (TGF)-β, one of the major profibrotic cytokines, induces the synthesis of plasminogen activator inhibitor (PAI)-1, a factor that plays a crucial role in the development of fibrosis. Here, we found that an isoprenoid antibiotic, ascofuranone, suppresses expression of profibrotic factors including matrix proteins and PAI-1 induced by TGF-β in renal fibroblasts. Ascofuranone selectively inhibits phosphorylation of epidermal growth factor receptor (EGFR), and downstream kinases such as Raf-1, MEK-1/2, and ERK-1/2. PAI-1 transcription also is suppressed by treatment with kinase inhibitors for MEK-1/2 or EGFR, and with small interfering RNA for EGFR. Ascofuranone inhibits cellular metalloproteinase activity, and an inhibitor of metalloproteinases suppresses EGFR phosphorylation and PAI-1 transcription. These results suggest that ascofuranone suppresses expression of profibrotic factors through the inhibition of an EGFR-dependent signal transduction pathway activated by metalloproteinases. J. Cell. Biochem. 107: 335–344, 2009. © 2009 Wiley-Liss, Inc." @default.
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- W2003203559 date "2009-03-20" @default.
- W2003203559 modified "2023-10-09" @default.
- W2003203559 title "Suppression of PAI-1 expression through inhibition of the EGFR-mediated signaling cascade in rat kidney fibroblast by ascofuranone" @default.
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- W2003203559 doi "https://doi.org/10.1002/jcb.22130" @default.
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