Rosiglitazone alleviates the persistent fibrotic phenotype of lesional skin scleroderma fibroblasts.
OBJECTIVE
The transcription factor peroxisome proliferator-activated receptor (PPAR)-gamma plays an important role in controlling cell differentiation. The aim of the present study was to examine whether PPAR-gamma expression was reduced in skin scleroderma fibroblasts and whether PPAR-gamma agonists could suppress the persistent fibrotic phenotype of skin scleroderma fibroblasts.


METHODS
Dermal fibroblasts were isolated from site-, age- and sex-matched healthy individuals and lesional areas of individuals with dcSSc. Western blot and collagen gel contraction analyses were used to detect protein expression in the presence or absence of the PPAR-gamma agonist rosiglitazone.


RESULTS
PPAR-gamma expression was reduced in dcSSc fibroblasts. The PPAR-gamma agonist rosiglitazone alleviated the persistent fibrotic phenotype of dcSSc fibroblasts.


CONCLUSIONS
Rosiglitazone may alleviate the extent of fibrosis in dcSSc.
Shi-wen
Xu
X
Centre for Rheumatology, University College London (Royal Free Campus), London, UK.
Eastwood
Mark
M
Stratton
Richard J
RJ
Denton
Christopher P
CP
Leask
Andrew
A
Abraham
David J
DJ
D000199:Actins / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D010641:Phenotype; D000077154:Rosiglitazone; D012594:Scleroderma, Localized / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D045162:Thiazolidinediones / Q000494:pharmacology*
C541116:ACTA2 protein, human; D000199:Actins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone