Gene expression profiles in systemic sclerosis tenosynovial biopsies

Systemic sclerosis is a connective tissue disease affecting skin and internal organs, characterized by a triad of inflammation, vasculopathy and progressive fibrosis, due to deposition of mainly type I collagen. Out of the intricate mechanisms involved in the pathogenesis of the disease, evidence indicates that TGFbeta signaling plays a central role in mediating the effects of several pro-fibrotic effectors. In addition, TGFbeta is induced by hypoxia in cultured fibroblasts, an observation suggesting a role for this cytokine in linking vasculopathy and fibrosis in the disease. Not surprisingly, TGFbeta and Wnt signaling are among the most prevalent pathways found in global gene expression studies performed on systemic sclerosis skin biopsies. In this perspective, modulation of TGFbeta activity remains a top therapeutic target in systemic sclerosis drug development.

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