Curcumin might be an effective antifibrotic drug in the treatment of chronic kidney disease.

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

Jens Gaedeke, Nancy A Noble, Wayne A Border

Kidney Int

Jul 1, 2004

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Abstract

BACKGROUND: Over-expression of transforming growth factor-beta (TGF-beta) 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-beta's profibrotic actions in vitro. METHODS: NRK49F rat renal fibroblasts were stimulated with TGF-beta (5 ng/mL), and the effects of curcumin on TGF-beta-regulated genes, TGF-beta 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-beta-regulated gene and protein expression were analyzed with RNAi. RESULTS: When applied 30 minutes before TGF-beta, curcumin dose dependently and dramatically reduced TGF-beta-induced increases in plasminogen activator inhibitor-1 (PAI-1), TGF-beta1, fibronectin (FN) and collagen I (Col I) mRNA, and in PAI-1 and fibronectin protein. Prolonged curcumin treatment (>6 h) significantly reduced TGF-beta receptor type II levels and SMAD2/3 phosphorylation in response to added TGF-beta. Depletion of cellular c-jun levels with a RNAi method mimicked the effects of curcumin on expression of TGF-beta1, FN, and Col I, but not PAI-1. CONCLUSION: Curcumin blocks TGF-beta's profibrotic actions on renal fibroblasts through down-regulation of TbetaRII, 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.