Inhibition of activator protein 1 signaling abrogates transforming growth factor beta-mediated activation of fibroblasts and prevents experimental fibrosis

Abstract

We demonstrate that AP-1 specify is upregulated in a TGF-Beta dependent manner in SSc and that inhibition of AP-1 reduces the collagen synthesis in SSc fibroblasts. The selective AP-1 inhibitor T-5224 efficiently prevented the development of dermal fibrosis in different mouse models of SSc.

Thus, AP-1 might be a promising new molecular target for the treatment of SSc.

Keywords

• systemic sclerosis
• experimental dermal fibrosis
• AP-1 signaling