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Regulation of 25‐hydroxyvitamin D‐1‐hydroxylase and 24‐hydroxylase in keratinocytes by PTH and FGF 23
Author(s) -
Wu Wenlin,
Fan Hong,
Jiang Yi,
Liao Liyan,
Li Lusha,
Zhao Juan,
Zhang Huiling,
Shrestha Chandrama,
Xie Zhongjian
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13760
Subject(s) - involucrin , hacat , loricrin , filaggrin , keratinocyte , protein kinase c , protein kinase a , chemistry , endocrinology , parathyroid hormone , mapk/erk pathway , fibroblast growth factor , medicine , microbiology and biotechnology , biology , kinase , biochemistry , immunology , calcium , in vitro , receptor , atopic dermatitis
Abstract Renal 25‐hydroxyvitamin D‐1α‐hydroxylase (1α OH ase, CYP 27B1) and 24‐hydroxylase (24 OH ase, CYP 24A1) are tightly regulated. However, little is known about the regulation of 1α( OH )ase and 24( OH )ase in extrarenal tissue such as the epidermis. This study was to determine the roles of parathyroid hormone ( PTH ) and fibroblast growth factor 23 ( FGF 23) in the regulation of 1α( OH )ase and 24( OH )ase in epidermal keratinocytes as well as epidermal keratinocyte proliferation and differentiation. The results showed that PTH increased the protein level of 1α( OH )ase in human epidermal keratinocyte cell line HaCaT, but had no effect on the level of 24( OH )ase. The effect of PTH on 1α( OH )ase was blocked by the PKC inhibitor. Treatment with FGF 23 decreased mRNA and protein levels of 1α( OH )ase and increased mRNA and protein levels of 24( OH )ase in HaCaT cells. The effect of FGF 23 on 1α( OH )ase and 24( OH )ase was blocked by the mitogen‐activated protein kinase/extracellular regulated protein kinase ( MAPK / ERK ) inhibitor. In addition, treatment with PTH enhanced levels of differentiation markers including keratin 1, involucrin, loricrin, and filaggrin but reduced levels of BrdU incorporation in HaCaT cells. These effects were inhibited by the PKC inhibitor. FGF 23 enhanced proliferation of HaCaT cells, but reduced levels of early differentiation markers including keratin 1 and involucrin and enhanced levels of the later differentiation markers including loricrin and filaggrin. These results suggest that PTH stimulates 1α( OH )ase expression and differentiation of HaCaT cells and inhibits proliferation via PKC . The data also suggest that FGF 23 inhibits 1α( OH )ase expression and stimulates 24( OH )ase expression via MAPK / ERK . In addition, FGF 23 enhances proliferation and late differentiation and inhibits early differentiation of HaCaT keratinocytes.