title: Low vitamin D-modulated calcium-regulating proteins in psoriasis vulgaris plaques: S100A7 overexpression depends on joint involvement.
abstract: Psoriasis is an inflammatory skin disease with or without joint involvement. In this disease, the thickened epidermis and impaired barrier are associated with altered calcium gradients. Calcium and vitamin D are known to play important roles in keratinocyte differentiation and bone metabolism. Intracellular calcium is regulated by calcium-sensing receptor (CASR), calcium release-activated calcium modulator (ORAI) and stromal interaction molecule (STIM). Other proteins modulated by vitamin D play important roles in calcium regulation e.g., calbindin 1 (CALB1) and transient receptor potential cation channel 6 (TRPV6). In this study, we aimed to investigate the expression of calcium-regulating proteins in the plaques of patients with psoriasis vulgaris with or without joint inflammation. We confirmed low calcium levels, keratinocyte hyperproliferation and an altered epidermal barrier. The CASR, ORAI1, ORAI3, STIM1, CALB1 and TRPV6 mRNA, as well as the sterol 27-hydroxylase (CYP27A1), 25-hydroxyvitamin D3 1-α-hydroxylase (CYP27B1) and 1,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1) protein levels were low in the plaques of patients with psoriasis. We demonstrated S100 calcium-binding protein A7 (S100A7) overexpression in the plaques of patients with psoriasis vulgaris with joint inflammation, compared with those without joint involvement. We suggest an altered capacity to regulate the intracellular Ca2+ concentration ([Ca2+]i), characterized by a reduced expression of CASR, ORAI1, ORAI3, STIM1, CALB1 and TRPV6 associated with diminished levels of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], which may be associated with an altered balance between keratinocyte proliferation and differentiation in the psoriatic epidermis. Additionally, differences in S100A7 expression depend on the presence of joint involvement.
authors: Department of Dermatology, Jena University Hospital, D-07743 Jena, Germany.
authors: Susana
authors: S
authors: Cubillos
authors: Department of Dermatology, Jena University Hospital, D-07743 Jena, Germany.
authors: Johannes
authors: J
authors: Norgauer
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007596:Joints / Q000473:pathology*; D015603:Keratinocytes / Q000473:pathology; D008875:Middle Aged; D011565:Psoriasis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D018167:Receptors, Calcitriol / Q000378:metabolism; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism*; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D018167:Receptors, Calcitriol; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D002118:Calcium