Animal models of scleroderma: fresh insights

Abstract

Recent years have seen the advent and progress in our understanding of fibrosis and vasculopathy in systemic sclerosis, scleroderma (SSc) largely mediated through the development and study of novel animal models. The most well studied animal models of SSc involve the bleomycin model of induced fibrosis and the Tsk/+ model. However, even though these models provide useful insights into the pathogenesis of fibrosis and vasculopathy, they do not mimic the disease accurately. Several mouse models have been developed that have specifically focused on the vasculopathy of SSc and have yielded relevant insights into this disorder further highlighting the novel mechanisms that may be responsible for this pathological feature. Furthermore, the contribution of the innate immune system mediated by the inflammasome in the induction of fibrosis has also demonstrated significant insights, possibly implicating an etiological mechanism of SSc. And recent transgenic or knockout animal models have emphasized the relevance of macrophage chemoattractant protein-1 (MCP-1), alpha-melanocyte stimulating hormone (α-MSH), and peroxisome proliferator-activated receptor-gamma (PPARγ) in fibrosis. Recent advances in animal models of SSc have elucidated the involvement of relevant proteins that appear to mediate vasculopathy and also implicated the involvement of the innate immune system in fibrosis. These models have identified novel therapeutic targets that may lead to more effective treatments for this incurable disease.