Inhibitory Effect of Mitoxantrone on Collagen Synthesis in Dermal Fibroblasts
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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 synthe- sis 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 trans- forming growth factor (TGF)-β-induced phosphorylation of SMAD3. Finally, mitoxan- trone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability. Conclusion: These results suggest that mitoxantrone reduces collagen synthesis by inhibit- ing TGF-β/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.
Abstract
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 synthe- sis 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 trans- forming growth factor (TGF)-β-induced phosphorylation of SMAD3. Finally, mitoxan- trone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability. Conclusion: These results suggest that mitoxantrone reduces collagen synthesis by inhibit- ing TGF-β/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.
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