Bleomycin inhibits adipogenesis and accelerates fibrosis in the subcutaneous adipose layer through TGF-ß1.

ABSTRACT

Systemic sclerosis [scleroderma (SSc)]-associated skin fibrosis is characterized by increased fibrosis in the dermis and a reduction in the thickness of the subcutaneous adipose tissue layer. Although many studies have examined fibrosis in SSc, only a few studies have focused on the associated reduction in the thickness of the subcutaneous adipose tissue layer. In this study, we investigated the effects of SSc-induced fibrosis on adipose tissue. We found that bleomycin suppresses adipogenesis in adipose-derived stem cells (ASCs) and stimulates ASCs to express transforming growth factor ß1 (TGF-ß1), which suppresses adipogenesis and promotes fibrosis. Furthermore, we found that adipocyte-conditioned medium suppressed collagen synthesis by fibroblasts in fibrosis-like conditions. We concluded that in the skin affected by bleomycin-induced fibrosis, increased TGF-ß1 expression suppresses adipogenesis and promotes adipocyte fibrosis. It was also suggested that adipocytes have an inhibitory effect on the progression of fibrosis.