Suppression of transforming growth factor beta/smad signaling in keloid-derived fibroblasts by quercetin: implications for the treatment of excessive scars.
BACKGROUND
Keloids are characterized by abnormal proliferation and overproduction of extracellular matrix. Quercetin, a dietary compound, has strong antioxidant and anticancer properties. Previous studies by the authors have shown that quercetin inhibits fibroblast proliferation, collagen production, and contraction of keloid and hypertrophic scar-derived fibroblasts. Quercetin also blocks the signal transduction of insulin-like growth factor-1 in keloid fibroblasts. This study assessed the effects of quercetin on the transforming growth factor (TGF)-beta/Smad-signaling pathway in keloid-derived fibroblasts, which may be an important biologic mechanism of this proliferative scarring.


METHODS
Keloid fibroblasts were isolated from keloid tissue specimens. Cells were treated with quercetin at different concentrations, then harvested, and subjected to immunoblotting analysis.


RESULTS
Quercetin significantly inhibited the expression of TGF-beta receptors 1 and 2 in keloid fibroblasts at three concentrations (low, medium, and high). Quercetin also strongly suppressed the basal expression of Smad2, Smad3, and Smad4 as well as the phosphorylation of Smad2 and Smad3 and the formation of the Smad2-Smad3-Smad4 complex.


CONCLUSIONS
Taken together, these data suggest that quercetin effectively blocks the TGF-beta/Smad-signaling pathway in keloid fibroblasts. These data indicate that quercetin-based therapies for keloids should be investigated further.
Phan
Toan-Thang
TT
Department of Plastic Surgery, Singapore General Hospital. surptt@nus.edu.sg
Lim
Ivor Jiun
IJ
Chan
Sui-Yung
SY
Tan
Ee-Kim
EK
Lee
Seng-Teik
ST
Longaker
Michael T
MT
D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002921:Cicatrix / Q000188:drug therapy*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D047468:Immunoprecipitation; D007627:Keloid / Q000503:physiopathology / Q000517:prevention & control*; D011794:Quercetin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D051785:Smad Proteins; D015534:Trans-Activators / Q000037:antagonists & inhibitors*
D000975:Antioxidants; D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D015534:Trans-Activators; D011794:Quercetin