Instituto de Biomedicina de Valencia (IBV), Consejo Superior de Investigaciones Científicas (CSIC), Jaime Roig 11, Valencia, Valencia, 46010, Spain.
Br J Pharmacol. 2022 Jul;179(13):3178-3189. doi: 10.1111/bph.15736. Epub 2021 Dec 23.
The mineralocorticoid receptor (MR or NR3C2) is expressed in all types of cells from the different skin compartments. The binding and activation by glucocorticoids has a higher affinity than that on the closely related glucocorticoid receptor (GR or NR3C1). As both corticosteroid receptors are co-express in the skin and considering the therapeutic relevance of glucocorticoids to combat skin inflammatory diseases, it was proposed that several of the major side effects of topical glucocorticoids, such as skin atrophy and delayed wound healing, were due to unintended activation of the MR. Indeed, cutaneous MR blockade using genetic and pharmacological approaches in mice and human reduced corticosteroid-associated skin atrophy in conditions of endogenous and pharmacological glucocorticoid excess. Although data support the safety of topical MR antagonists combined with glucocorticoid, it is crucial to address the efficacy of treatment in skin inflammatory conditions and its impact on the overall metabolism. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.
盐皮质激素受体（MR 或 NR3C2）在不同皮肤部位的所有类型细胞中均有表达。糖皮质激素的结合和激活比密切相关的糖皮质激素受体（GR 或 NR3C1）具有更高的亲和力。由于两种皮质类固醇受体在皮肤中均有共表达，并且考虑到糖皮质激素在治疗皮肤炎症性疾病方面的重要性，因此有人提出，局部糖皮质激素的许多主要副作用，如皮肤萎缩和伤口愈合延迟，是由于 MR 的意外激活。事实上，在小鼠和人类中，通过遗传和药理学方法阻断皮肤 MR，减少了内源性和药理学糖皮质激素过多情况下与皮质类固醇相关的皮肤萎缩。尽管数据支持局部 MR 拮抗剂与糖皮质激素联合使用的安全性，但在皮肤炎症情况下，治疗的疗效及其对整体代谢的影响至关重要。相关文章：本文是醛固酮-盐皮质激素受体信号通路治疗靶向新兴领域专题的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc/。
