title: Calcium--a central regulator of keratinocyte differentiation in health and disease.
abstract: 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.
authors.affiliation: Department of Pharmacology, Biocenter, Goethe University, Frankfurt, Germany.
authors.forename: Floriana
authors.initials: F
authors.lastname: Elsholz
authors.affiliation: Institute of Pharmacology and Toxicology & Interfaculty Centre for Pharmacogenomics and Drug Research Eberhard-Karls-University, Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Harteneck
authors.affiliation: Department of Pharmacology, Biocenter, Goethe University, Frankfurt, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Muller
authors.affiliation: Department of Molecular and Clinical Pharmacy, Friedrich-Alexander University Erlangen/Nuremberg, Cauerstr. 4, 91058 Erlangen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Friedland
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D007644:Darier Disease / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D000071740:ORAI1 Protein; D011565:Psoriasis / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D012871:Skin Diseases / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D044169:Receptors, Calcium-Sensing; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D050051:Transient Receptor Potential Channels; D002118:Calcium
keywords: TRP channels; calcium; differentiation; keratinocyte