Abstract
Introduction: 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.
Original language | English (US) |
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Article number | R102 |
Journal | Arthritis Research and Therapy |
Volume | 14 |
Issue number | 3 |
DOIs | |
State | Published - May 1 2012 |
Funding
We are grateful to Alexander Misharin for technical help. This work was supported by grants from the Association for the Development of Rheumatology (Slovenia), the Ministry of High Education, Science and Technology of Slovenia (grant P3-0314), the National Institutes of Health, the Scleroderma Research Foundation, and the Karen Brown Scleroderma Foundation.
ASJC Scopus subject areas
- Rheumatology
- Immunology and Allergy
- Immunology