E3 ubiquitin ligase: A potential regulator in fibrosis and systemic sclerosis

• E3 ubiquitin ligases participate in the regulation of TGF-β signaling.
• E3 ubiquitin ligases involve in fibrosis through TGF-β signaling.
• E3 ubiquitin ligases regulate fibrosis through other mechanisms.
• The role of E3 ligases played in SSc may lead to novel pharmacologic therapies.

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis in the skin and internal organs. The pathogenesis of SSc is not completely understood until now. Recently, many studies have focused on the role of E3 ubiquitin ligases in organ fibrosis. However, the possible regulatory mechanisms of E3 ubiquitin ligases in fibrosis and SSc are not well documented. In this review, we summarized that E3 ubiquitin ligases regulated fibrosis through ubiquitin-mediated degradation of TGF-β/Smad signaling pathway. Moreover, E3 ubiquitin ligases participated in regulating fibrosis by other methods, such as inducing epithelial transition to mesenchymal cell, enhancing the production of TGF-β and protecting activated hepatic stellate cells from apoptosis. However, the specific regulatory mechanisms of E3 ubiquitin ligases in scleroderma is still not fully understood. There are more works to be done to specify the mechanism of E3 ubiquitin ligases in regulation of fibrosis in SSc.