Troglitazone suppresses transforming growth factor-beta1-induced collagen type I expression in keloid fibroblasts.
BACKGROUND
Peroxisome proliferator-activated receptor (PPAR)-gamma agonists are increasingly used in patients with diabetes and some studies have suggested a beneficial effect on organ fibrosis. However their effects on dermal fibrosis in keloids are unknown.


OBJECTIVE
To investigate the effect of the PPAR-gamma agonist troglitazone on transforming growth factor (TGF)-beta1-induced collagen type I expression in keloid fibroblasts.


METHODS
Keloid fibroblasts were cultured and exposed to different concentrations of troglitazone in the presence of TGF-beta1. The mRNA expression of PPAR-gamma was determined by semiquantitative reverse transcriptase-polymerase chain reaction. The protein of PPAR-gamma, Smad2, Smad3, phoshpo-Smad2/3 and collagen type I was determined by Western blotting and collagen synthesis was evaluated by measuring (3)H-proline incorporation. The effect of troglitazone on cell viability was evaluated by the colorimetric conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide.


RESULTS
PPAR-gamma was expressed at a moderate level in keloid fibroblasts. Troglitazone depressed TGF-beta1-stimulated collagen type I expression and collagen synthesis in keloid fibroblasts in a concentration-dependent manner. Moreover, troglitazone inhibited expression and phosphorylation of TGF-beta1-induced Smad2/3. Cell viability was unaffected. These inhibitory effects of troglitazone were reversed by the PPAR-gamma-specific antagonist GW9662.


CONCLUSIONS
Our data suggest that PPAR-gamma is present in keloid fibroblasts and PPAR-gamma activation inhibits TGF-beta1-induced collagen type I expression at least in part by decreasing collagen synthesis. PPAR-gamma may be a promising therapeutic target for keloids.
Zhang
G-Y
GY
Department of Hand and Plastic Surgery, Second Affiliated Hospital of Wenzhou Medical College, Xueyuan West Road 109, Wenzhou 325027, Zhejiang Province, China. guoyou.zhang@yahoo.com
Yi
C-G
CG
Li
X
X
Ma
B
B
Li
Z-J
ZJ
Chen
X-L
XL
Guo
S-Z
SZ
Gao
W-Y
WY
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002839:Chromans / Q000627:therapeutic use*; D024042:Collagen Type I / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007627:Keloid / Q000378:metabolism*; D008297:Male; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000077288:Troglitazone; D055815:Young Adult
D002839:Chromans; D024042:Collagen Type I; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D051785:Smad Proteins; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D000077288:Troglitazone