Ann Dermatol.  2022 Jun;34(3):206-211. 10.5021/ad.2022.34.3.206.

Inhibitory Effect of Mitoxantrone on Collagen Synthesis in Dermal Fibroblasts

• Kim KI
• Kwon CI
• Lee JH
• Kim CD
• Yoon TJ

• KMID: 2530022
• DOI: http://doi.org/10.5021/ad.2022.34.3.206

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 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.

Keyword

Collagen; Fibroblasts; LARP6; Mitoxantrone; SMAD