title: Curcumin inhibits transforming growth factor-beta activity via inhibition of Smad signaling in HK-2 cells.
abstract: 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.
authors.affiliation: Department of Nephrology, Second Affiliated Hospital, Zhe Jiang University School of Medicine, Hangzhou, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Hua
authors.initials: H
authors.lastname: Liang
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xuanding
authors.initials: X
authors.lastname: Wang
mesh_terms: D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects*; D015398:Signal Transduction; D051785:Smad Proteins / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D003474:Curcumin