Schmuth Matthias, Moosbrugger-Martinz Verena, Blunder Stefan, Dubrac Sandrine
Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
Biochim Biophys Acta. 2014 Mar;1841(3):463-73. doi: 10.1016/j.bbalip.2013.11.012. Epub 2013 Dec 3.
Epidermal lipid synthesis and metabolism are regulated by nuclear hormone receptors (NHR) and in turn epidermal lipid metabolites can serve as ligands to NHR. NHR form a large superfamily of receptors modulating gene transcription through DNA binding. A subgroup of these receptors is ligand-activated and heterodimerizes with the retinoid X receptor including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR) and pregnane X receptor (PXR). Several isotypes of these receptors exist, all of which are expressed in skin. In keratinocytes, ligand activation of PPARs and LXRs stimulates differentiation, induces lipid accumulation, and accelerates epidermal barrier regeneration. In the cutaneous immune system, ligand activation of all three receptors, PPAR, LXR, and PXR, has inhibitory properties, partially mediated by downregulation of the NF-kappaB pathway. PXR also has antifibrotic effects in the skin correlating with TGF-beta inhibition. In summary, ligands of PPAR, LXR and PXR exert beneficial therapeutic effects in skin disease and represent promising targets for future therapeutic approaches in dermatology. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
表皮脂质的合成与代谢受核激素受体（NHR）调控，反过来，表皮脂质代谢产物可作为NHR的配体。NHR构成了一个庞大的受体超家族，通过与DNA结合来调节基因转录。这些受体的一个亚组是配体激活型的，可与视黄醇X受体形成异二聚体，包括过氧化物酶体增殖物激活受体（PPAR）、肝X受体（LXR）和孕烷X受体（PXR）。这些受体存在多种同种型，均在皮肤中表达。在角质形成细胞中，PPAR和LXR的配体激活可刺激分化、诱导脂质积累并加速表皮屏障再生。在皮肤免疫系统中，PPAR、LXR和PXR这三种受体的配体激活均具有抑制特性，部分是通过下调NF-κB途径介导的。PXR在皮肤中还具有抗纤维化作用，与抑制转化生长因子-β相关。总之，PPAR、LXR和PXR的配体在皮肤病中发挥有益的治疗作用，是皮肤病未来治疗方法的有前景的靶点。本文是名为“脂质在表皮中的重要作用及其在皮肤屏障形成和维持中的作用”特刊的一部分。客座编辑：肯尼斯·R·费因戈尔德和彼得·埃利亚斯。
