title: Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker?
abstract: BACKGROUND
  Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses in vitro and in vivo. Reduced expression and function of PPAR-gamma in patients with SSc may contribute to progression of fibrosis. Here we evaluated the levels of adiponectin, a sensitive and specific index of PPAR-gamma activity, as a potential fibrogenic biomarker in SSc.
  
  
  METHODS
  Adiponectin levels were determined in the sera of 129 patients with SSc and 86 healthy controls, and serial determinations were performed in 27 patients. Levels of adiponectin mRNA in skin biopsies from SSc patients were assessed in an expression profiling microarray dataset. Regulation of adiponectin gene expression in explanted human subcutaneous preadipocytes and fibroblasts was examined by real-time quantitative PCR.
  
  
  RESULTS
  Patients with diffuse cutaneous SSc had reduced serum adiponectin levels. A significant inverse correlation between adiponectin levels and the modified Rodnan skin score was observed. In longitudinal studies changes in serum adiponectin levels were inversely correlated with changes in skin fibrosis. Skin biopsies from a subset of SSc patients showed reduced adiponectin mRNA expression which was inversely correlated with the skin score. An agonist ligand of PPAR-gamma potently induced adiponectin expression in explanted mesenchymal cells in vitro.
  
  
  CONCLUSIONS
  Levels of adiponectin, reflecting PPAR-gamma activity, are correlated with skin fibrosis and might have potential utility as a biomarker in SSc.
authors.affiliation: Department of Rheumatology, University Medical Centre Ljubljana, Vodnikova 62, Ljubljana 1000, Slovenia. katja.lakota@guest.arnes.si
authors.forename: Katja
authors.initials: K
authors.lastname: Lakota
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Mary
authors.initials: M
authors.lastname: Carns
authors.forename: Monique
authors.initials: M
authors.lastname: Hinchcliff
authors.forename: Jungwha
authors.initials: J
authors.lastname: Lee
authors.forename: Michael L
authors.initials: ML
authors.lastname: Whitfield
authors.forename: Snezna
authors.initials: S
authors.lastname: Sodin-Semrl
authors.forename: John
authors.initials: J
authors.lastname: Varga
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis / Q000097:blood*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000097:blood* / Q000473:pathology*; D012867:Skin / Q000473:pathology*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D047495:PPAR gamma