title: Curcumin suppresses TGF-β signaling by inhibition of TGIF degradation in scleroderma fibroblasts.
abstract: 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.
authors.affiliation: Department of Dermatology and Venerology, Beijing Military Command General Hospital of PLA, China.
authors.forename: Kemin
authors.initials: K
authors.lastname: Song
authors.forename: Shaowen
authors.initials: S
authors.lastname: Peng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Rongya
authors.initials: R
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000378:metabolism*; D051899:Smad2 Protein / Q000037:antagonists & inhibitors; D051900:Smad3 Protein / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D051899:Smad2 Protein; D051900:Smad3 Protein; C097504:TGIF1 protein, human; D016212:Transforming Growth Factor beta; D003474:Curcumin