Department of Dermatology, University of California San Diego, La Jolla, California, USA.
Department of Dermatology, University of California San Diego, La Jolla, California, USA.
J Invest Dermatol. 2024 Jan;144(1):84-95.e3. doi: 10.1016/j.jid.2023.07.009. Epub 2023 Aug 5.
Absorption of dietary iron is largely regulated by the liver hormone hepcidin, which is released under conditions of iron overload and inflammation. Although hepcidin-dependent regulation of iron uptake and circulation is well-characterized, recent studies have suggested that the skin may play an important role in iron homeostasis, including transferrin receptor-mediated epidermal iron uptake and direct hepcidin production by keratinocytes. In this study, we characterized direct keratinocyte responses to conditions of high and low iron. We observed potent iron storage capacity by keratinocytes in vitro and in vivo and the effects of iron on epidermal differentiation and gene expression associated with inflammation and barrier function. In mice, systemic iron was observed to be coupled to epidermal iron content. Furthermore, topical inflammation, as opposed to systemic inflammation, resulted in a primary iron-deficiency phenotype associated with low liver hepcidin. These studies suggest a role for keratinocytes and epidermal iron storage as regulators of iron homeostasis with direct contribution by the cutaneous inflammatory state.
膳食铁的吸收在很大程度上受肝脏激素铁调素的调节，铁调素在铁过载和炎症条件下释放。尽管铁调素依赖性铁摄取和循环的调节已得到很好的描述，但最近的研究表明，皮肤可能在铁稳态中发挥重要作用，包括转铁蛋白受体介导的表皮铁摄取和角蛋白细胞直接产生铁调素。在这项研究中，我们描述了角蛋白细胞对高和低铁条件的直接反应。我们观察到体外和体内角蛋白细胞具有很强的铁储存能力，以及铁对与炎症和屏障功能相关的表皮分化和基因表达的影响。在小鼠中，观察到系统铁与表皮铁含量相关。此外，与系统性炎症相反，局部炎症导致与低肝铁调素相关的原发性缺铁表型。这些研究表明角蛋白细胞和表皮铁储存作为铁稳态调节剂的作用，其直接贡献来自皮肤炎症状态。
