Decorin Is Significantly Overexpressed in Nephrogenic Systemic Fibrosis

The role of the proteoglycans in the pathogenesis of nephrogenic systemic fibrosis (NSF) is unclear. We assessed expression of decorin, versican, and transforming growth factor β1 (TGF-β1) in skin specimens of 10 patients with biopsy-proven NSF and different control groups. Real-time reverse transcription–polymerase chain reaction studies and immunohistochemical analysis were performed on full-thickness skin specimens. The messenger RNA (mRNA) and protein levels of decorin were significantly higher in the skin lesions of patients with NSF than in skin lesions of patients with systemic sclerosis, patients undergoing hemodialysis, and healthy subjects. The versican mRNA levels in NSF lesions differed significantly only from the levels in healthy subjects. TGF-β1 mRNA expression was significantly overexpressed in NSF lesions compared with control skin specimens investigated. In NSF specimens, the mRNA expression of TGF-β1 and decorin were highly correlated (r = 0.92). Our results suggest that decorin and TGF-β1 may have a fundamental role in the pathogenesis of NSF. Conversely, versican seems less likely to be of pathogenetic significance in NSF. Nephrogenic systemic fibrosis (NSF) is an uncommon fibrosing disorder exclusively affecting patients with acute or chronic severe renal insufficiency after administration of linear gadolinium contrast agents. Common cutaneous manifestations include symmetric skin tightening and induration, particularly on lower extremities and forearms, less frequently involving the trunk or inner organs. The disease often progresses to joint contractures and immobility. 1-4 The 24-month mortality rate is described as up to 48%. 5 An association between linear gadolinium contrast agents and NSF has been reported in numerous series. In the skin, the diagnosis of NSF is strongly supported by histologic evidence of thickened collagen bundles, an increased number of CD34+ dermal fibrocytes, and mucin deposition. Two hypotheses have been offered to explain the pathogenesis of this uncommon fibrosis. The first involves infiltrating CD68+/XIIIa+ dendritic cells that synthesize local transforming growth factor β (TGF-β), a profibrotic cytokine. The second hypothesis involves bone marrow–derived CD45RO+/ CD34+/collagen I–positive circulatory fibrocytes that are recruited to the skin, yielding fibrosis. 2,3,6 Alteration of the extracellular matrix (ECM), in particular overexpression of mucin, has consistently been reported in NSF. 1-4 However, the role of the proteoglycans in the pathogenesis of NSF has not been addressed in previous studies. The aim of this study was to evaluate the expression of decorin and versican in skin specimens of NSF and different control groups.