Dermal tissue and cellular expression of fibrillin-1 in diffuse cutaneous systemic sclerosis

Objective. To assess dermal expression and fibroblast production of fibrillin-1 (FBN-1) in SSc. Methods. In vivo analysis of microfibrillar network was performed using EM from affected and unaffected skin biopsy specimens of dcSSc patients (n = 5) compared with healthy controls (n = 2). FBN-1 matrix deposition and organization by dermal fibroblast cultures from dcSSc (n = 6), healthy (n = 5) and Marfan (n = 4) controls was analysed in vitro by IF with or without TGF-b activation. Finally, production of FBN-1 by cultured dermal fibroblasts was evaluated by western blot (WB) and real-time PCR. Results. We observed a striking decrease of tissue microfibrillar network in the dermis of SSc patients compared with healthy controls affecting both clinically involved and uninvolved skin. In cultures, SSc dermal fibroblasts displayed no apparent in vitro alteration of synthesis, secretion and organization of microfibril network. The WB and real-time PCR analyses showed similar FBN-1 amounts in matrix and FBN1 gene expression in SSc and healthy controls. Conclusions. We observed a striking decrease of in vivo microfibrillar network in clinically affected and unaffected skin in early dcSSc patients. This does not relate to an inability of SSc dermal fibroblasts to produce, secrete and organize microfibrils in vitro. Therefore, the disturbances of microfibrils in SSc may be a secondary event to matrix remodelling that occurs in this disease.