Inhibitory Effect of Mitoxantrone on Collagen Synthesis in Dermal Fibroblasts

BACKGROUND: Fibroblasts produce collagen molecules that support the structure of the skin. The decrease and hypersynthesis of collagen causes skin problems such as skin atrophy, wrinkles and scars. OBJECTIVE: The purpose of this study is to investigate the mechanism of mitoxantrone on collagen synthesis in fibroblasts. METHODS: Cultured fibroblasts were treated with mitoxantrone, and then collagen synthesis was confirmed by reverse transcription-polymerase chain reaction and Western blot. RESULTS: Mitoxantrone inhibited the expression of type I collagen in fibroblasts at both the mRNA and protein levels. In the collagen gel contraction assay, mitoxantrone significantly inhibited gel contraction compared to the control group. Mitoxantrone inhibited transforming growth factor (TGF)-β-induced phosphorylation of SMAD3. Finally, mitoxantrone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability. CONCLUSION: These results suggest that mitoxantrone reduces collagen synthesis by inhibiting TGF-β/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.