Curcumin suppresses TGF-β signaling by inhibition of TGIF degradation in scleroderma fibroblasts

Biochem Biophys Res Commun. 2011 Aug 12;411(4):821-5. doi: 10.1016/j.bbrc.2011.07.044. Epub 2011 Jul 21.


The transforming growth factor-β (TGF-β) signaling pathway plays a key role in the fibrotic process in systemic scleroderma (SSc). Curcumin, a Turmeric root extract, has been demonstrated to exert antifibrotic activity. In the present study, we carefully investigated the effect of curcumin on TGF-β signaling and its potential mechanism in SSc fibroblasts. We demonstrated a potent inhibitory effect of curcumin on TGF-β signaling. Curcumin counteracted TGF-β-induced phosphorylation of Smad2 but not Smad3. Further study revealed curcumin induced upregulation of TGF-β-induced factor (TGIF), a negative regulator of TGF-β signaling. The TGIF silencing results evidenced the essential role of TGIF in curcumin-mediated TGF-β/Smad2 suppression. Moreover, our data indicated that the upregulation of TGIF by curcumin might result from decreased ubiquitination of TGIF, which blocks its proteasome-mediated degradation. Collectively, our data provide a novel mechanism of curcumin-mediated suppression of fibrotic process in scleroderma.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cells, Cultured
  • Curcumin / pharmacology*
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Homeodomain Proteins / metabolism*
  • Humans
  • Middle Aged
  • Phosphorylation / drug effects
  • Repressor Proteins / metabolism*
  • Scleroderma, Systemic / metabolism*
  • Smad2 Protein / antagonists & inhibitors
  • Smad3 Protein / antagonists & inhibitors
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Up-Regulation


  • Antineoplastic Agents
  • Homeodomain Proteins
  • Repressor Proteins
  • Smad2 Protein
  • Smad3 Protein
  • TGIF1 protein, human
  • Transforming Growth Factor beta
  • Curcumin