Curcumin inhibits transforming growth factor-beta activity via inhibition of Smad signaling in HK-2 cells.

BACKGROUND

Curcumin, a polyphenolic compound derived from rhizomes of Curcuma spp., has been shown to possess potent anti-fibrotic properties. Here, we investigate the role of curcumin in modulating the profibrotic action of TGF-beta in human proximal tubule cells (HK-2) and its underlying mechanisms.

METHODS

HK-2 cells were stimulated with 5 ng/ml TGF-beta(1). The effects of curcumin on TGF-beta(1)-regulated gene expression and Smad phosphorylation were analyzed by RT-PCR, ELISA and Western blotting.

RESULTS

Curcumin inhibited TGF-beta(1)-induced plasminogen activator inhibitor-1 (PAI-1), alpha-smooth muscle actin (alpha-SMA) mRNA and protein expression. Curcumin suppressed not only TGF-beta(1)-induced Smad2 phosphorylation in a dose- and time-dependent manner, but also the nuclear accumulation of receptor-regulated Smads (R-Smad), Smad2 and Smad3. A serine/threonine protein phosphatase inhibitor (microcystin) could partly reverse the inhibitory effect of curcumin on Smad phosphorylation.

CONCLUSIONS

Curcumin blocks the profibrotic actions of TGF-beta on HK-2 cells through the down-regulation of the Smad signaling pathway, and curcumin may have some similar effect as serine/threonine protein phosphatases. Our findings suggest curcumin as a potential candidate for treatment of tubulointerstitial fibrosis.