Decreased cathepsin V expression due to Fli1 deficiency contributes to the development of dermal fibrosis and proliferative vasculopathy in systemic sclerosis.
The expression of friend leukemia integration factor 1 (Fli1), a transcriptional repressor of collagen, was increased after treatment with ciprofloxacin only in SSc fibroblasts, and this was accompanied by a decrease in the levels of DNA methyltransferase 1 (Dnmt1).
Western blot analysis of cell lysates demonstrated that the levels of phospho-Fli-1 (Thr312) were up-regulated in SSc fibroblasts, correlating with increased levels of type I collagen and c-Abl protein.
In this article, we review the impact of Fli1 deficiency on the pathogenesis of SSc and discuss a new therapeutic strategy for SSc by targeting the transcription factor Fli1.
Fli1 regulates genes that are involved in vessel maturation and stabilization, suggesting that reduced levels of Fli1 in SSc vasculature could contribute to the development of unstable vessels that are prone to regression.
In contrast to healthy skin, Fli1 protein is consistently absent from fibroblasts and significantly reduced in endothelial cells in clinically involved scleroderma skin, which correlates with enhanced collagen synthesis in systemic sclerosis skin.