PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
 
Arthritis Res Ther. 2012; 14(3): R144.
Published online Jun 13, 2012. doi:  10.1186/ar3877
PMCID: PMC3446527
CD109, a TGF-β co-receptor, attenuates extracellular matrix production in scleroderma skin fibroblasts
Xiao-Yong Man,1 Kenneth W Finnson,1 Murray Baron,2 and Anie Philipcorresponding author1
1Division of Plastic Surgery, Department of Surgery, McGill University, Montreal General Hospital, 1650 Cedar Avenue, Montreal, H3G 1A4,Canada
2Department of Rheumatology, McGill University, Jewish General Hospital, 3755 Cote St Catherine Road, Montreal, H3T 1E2,Canada
corresponding authorCorresponding author.
Xiao-Yong Man: manxyzju/at/yahoo.com; Kenneth W Finnson: kenneth.finnson/at/gmail.com; Murray Baron: mbaron/at/rhu.jgh.mcgill.ca; Anie Philip: anie.philip/at/mcgill.ca
Received August 31, 2011; Revised May 3, 2012; Accepted June 13, 2012.
Abstract
Introduction
Scleroderma or systemic sclerosis (SSc) is a complex connective tissue disease characterized by fibrosis of skin and internal organs. Transforming growth factor beta (TGF-β) plays a key role in the pathogenesis of SSc fibrosis. We have previously identified CD109 as a novel TGF-β co-receptor that inhibits TGF-β signaling. The aim of the present study was to determine the role of CD109 in regulating extracellular matrix (ECM) production in human SSc skin fibroblasts.
Methods
CD109 expression was determined in skin tissue and cultured skin fibroblasts of SSc patients and normal healthy subjects, using immunofluorescence, western blot and RT-PCR. The effect of CD109 on ECM synthesis was determined by blocking CD109 expression using CD109-specific siRNA or addition of recombinant CD109 protein, and analyzing the expression of ECM components by western blot.
Results
The expression of CD109 proteinis markedly increased in SSc skin tissue in vivo and in SSc skin fibroblasts in vitro as compared to their normal counterparts. Importantly, both SSc and normal skin fibroblasts transfected with CD109-specific siRNA display increased fibronectin, collagen type I and CCN2 protein levels and enhanced Smad2/3 phosphorylation compared with control siRNA transfectants. Furthermore, addition of recombinant CD109 protein decreases TGF-β1-induced fibronectin, collagen type I and CCN2 levels in SSc and normal fibroblasts.
Conclusion
The upregulation of CD109 protein in SSc may represent an adaptation or consequence of aberrant TGF-β signaling in SSc. Our finding that CD109 is able to decrease excessive ECM production in SSc fibroblasts suggest that this molecule has potential therapeutic value for the treatment of SSc.
Articles from Arthritis Research & Therapy are provided here courtesy of
BioMed Central