TITLE

Curcumin blocks multiple sites of the TGF-β signaling cascade in renal cells

AUTHOR(S)
Gaedeke, Jens; Noble, Nancy A.; Border, Wayne A.
PUB. DATE
July 2004
SOURCE
Kidney International;Jul2004, Vol. 66 Issue 1, p112
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Curcumin blocks multiple sites of the TGF-β signaling cascade in renal cells. Background. Over-expression of transforming growth factor-β (TGF-β) contributes greatly to fibrotic kidney disease. The activator protein-1 (AP-1) inhibitor curcumin, a polyphenolic compound derived from Curcuma longa, has been shown to reduce collagen accumulation in experimental pulmonary fibrosis. Here, we investigate curcumin's ability to modulate TGF-β's profibrotic actions in vitro. Methods. NRK49F rat renal fibroblasts were stimulated with TGF-β (5 ng/mL), and the effects of curcumin on TGF-β–regulated genes, TGF-β receptors, and phosphorylated SMAD isoforms were analyzed by Northern blotting, enzyme-linked immunosorbent assay (ELISA), and Western blotting. The effects of c-jun depletion on TGF-β–regulated gene and protein expression were analyzed with RNAi. Results. When applied 30 minutes before TGF-β, curcumin dose dependently and dramatically reduced TGF-β–induced increases in plasminogen activator inhibitor-1 (PAI-1), TGF-β1, fibronectin (FN) and collagen I (Col I) mRNA, and in PAI-1 and fibronectin protein. Prolonged curcumin treatment (>6 h) significantly reduced TGF-β receptor type II levels and SMAD2/3 phosphorylation in response to added TGF-β. Depletion of cellular c-jun levels with a RNAi method mimicked the effects of curcumin on expression of TGF-β1, FN, and Col I, but not PAI-1. Conclusion. Curcumin blocks TGF-β's profibrotic actions on renal fibroblasts through down-regulation of TβRII, and through partial inhibition of c-jun activity. These in vitro data suggest that curcumin might be an effective antifibrotic drug in the treatment of chronic kidney disease.
ACCESSION #
13347246

 

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