Molecular pathogenesis of skin fibrosis: insight from animal models

Skin fibrosis occurs in a variety of human diseases, most notably systemic sclerosis (SSc). The end stage of scleroderma in human skin consists of excess collagen deposition in the dermis with loss of adnexal structures and associated adipose tissue. The initiating factors for this process and the early stages are believed to occur through vascular injury and immune dysfunction with a dysregulated inflammatory response. However, because of the insidious onset of the disease, this stage is rarely observed in humans and remains poorly understood. Animal models have provided a means to examine these early stages and to isolate and understand the effect of perturbations in signaling pathways, chemokines, and cytokines. This article summarizes recent progress in the understanding of the molecular pathogenesis of skin fibrosis in SSc from different animal models, both its initiation and its maintenance phases.