Elsholz Floriana, Harteneck Christian, Muller Walter, Friedland Kristina
Department of Pharmacology, Biocenter, Goethe University, Frankfurt, Germany.
Institute of Pharmacology and Toxicology & Interfaculty Centre for Pharmacogenomics and Drug Research Eberhard-Karls-University, Tübingen, Germany.
Eur J Dermatol. 2014 Nov-Dec;24(6):650-61. doi: 10.1684/ejd.2014.2452.
Regular keratinocyte differentiation is crucial for the formation of an intact epidermal barrier and is triggered by extracellular calcium. Disturbances of epidermal barrier formation and aberrant keratinocyte differentiation are involved in the pathophysiology of several skin diseases, such as psoriasis, atopic dermatitis, basal and squamous skin cancer, and genetic skin diseases such as Darier's disease and Olmstedt syndrome. In this review, we summarize current knowledge about the underlying molecular mechanisms of calcium-induced differentiation in keratinocytes. We provide an overview of calcium's genomic and non-genomic mechanisms to induce differentiation and discuss the calcium gradient in the epidermis, giving rise to cornified skin and lipid envelope formation. We focus on the calcium-sensing receptor, transient receptor potential channels, and STIM/Orai as the major constituents of calcium sensing and calcium entry in the keratinocytes. Finally, skin diseases linked to impaired differentiation will be discussed, paying special attention to disturbed TRP channel expression and TRP channel mutations.
正常的角质形成细胞分化对于完整的表皮屏障形成至关重要，且由细胞外钙触发。表皮屏障形成的紊乱和异常的角质形成细胞分化参与了多种皮肤病的病理生理过程，如银屑病、特应性皮炎、基底和鳞状皮肤癌，以及遗传性皮肤病如 Darier 病和 Olmstedt 综合征。在本综述中，我们总结了目前关于角质形成细胞中钙诱导分化的潜在分子机制的知识。我们概述了钙诱导分化的基因组和非基因组机制，并讨论了表皮中的钙梯度，其导致角质化皮肤和脂质包膜的形成。我们重点关注钙敏感受体、瞬时受体电位通道以及 STIM/Orai，它们是角质形成细胞中钙感知和钙内流的主要组成部分。最后，将讨论与分化受损相关的皮肤病，特别关注 TRP 通道表达的紊乱和 TRP 通道突变。
