Skin Research Institute of Singapore, Agency for Science, Technology and Research, Biomedical Grove, Immunos, Singapore.
Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, National University Hospital and National University of Singapore, Kent Ridge Wing, Singapore.
J Invest Dermatol. 2020 Oct;140(10):2032-2040.e1. doi: 10.1016/j.jid.2020.02.009. Epub 2020 Feb 28.
Hyperpigmentary conditions can arise when melanogenesis in the epidermis is misregulated. Understanding the pathways underlying melanogenesis is essential for the development of effective treatments. Here, we report that a group of metabolites called polyamines are important in the control of melanogenesis in human skin. Polyamines are cationic molecules present in all cells and are essential for cellular function. We report that polyamine regulator ODC1 is upregulated in melanocytes from melasma lesional skin. We report that the polyamine putrescine can promote pigmentation in human skin explants and primary normal human epidermal melanocytes through induction of tyrosinase which is rate-limiting for the synthesis of melanin. Putrescine supplementation on normal human epidermal melanocytes results in the activation of polyamine catabolism, which results in increased intracellular HO Polyamine catabolism is also increased in human skin explants that have been treated with putrescine. We further report that inhibition of polyamine catabolism prevents putrescine-induced promotion of tyrosinase levels and pigmentation in normal human epidermal melanocytes, showing that polyamine catabolism is responsible for the putrescine induction of melanogenesis. Our data showing that putrescine promotes pigmentation has important consequences for hyperpigmented and hypopigmented conditions. Further understanding of how polyamines control epidermal pigmentation could open the door for the development of new therapeutics.
当表皮中的黑色素生成失调时，就会出现色素沉着过度的情况。了解黑色素生成的途径对于开发有效的治疗方法至关重要。在这里，我们报告一组称为多胺的代谢物在人类皮肤黑色素生成的控制中起着重要作用。多胺是存在于所有细胞中的阳离子分子，对细胞功能至关重要。我们报告说，多胺调节剂 ODC1 在黄褐斑皮损皮肤的黑素细胞中上调。我们报告说，多胺腐胺可以通过诱导限速酶酪氨酸酶来促进人皮肤外植体和原代正常人表皮黑素细胞的色素沉着，酪氨酸酶是黑色素合成的限速酶。腐胺补充正常人表皮黑素细胞会导致多胺分解代谢的激活，从而导致细胞内 HO 增加。用腐胺处理的人皮肤外植体中的多胺分解代谢也增加。我们进一步报告说，抑制多胺分解代谢可防止腐胺诱导正常人表皮黑素细胞中酪氨酸酶水平和色素沉着的增加，表明多胺分解代谢是腐胺诱导黑色素生成的原因。我们的数据表明腐胺促进色素沉着，这对色素沉着过度和色素沉着不足的情况有重要影响。进一步了解多胺如何控制表皮色素沉着可能为开发新的治疗方法开辟道路。
