Transcriptional Regulation of 25-Hydroxyvitamin D-24-Hydroxylase (CYP24A1) by Calcemic Factors in Keratinocytes

• KANEMOTO Yoshiaki

  Research Institute of Innovative Medicine, Tokiwa Foundation Graduate School of Life Science and Engineering, Iryo Sosei University

• HAYAKAWA Akira

  Research Institute of Innovative Medicine, Tokiwa Foundation Graduate School of Life Science and Engineering, Iryo Sosei University

• SAWADA Takahiro

  Research Institute of Innovative Medicine, Tokiwa Foundation Graduate School of Life Science and Engineering, Iryo Sosei University

• AMANO Rei

  Research Institute of Innovative Medicine, Tokiwa Foundation Graduate School of Life Science and Engineering, Iryo Sosei University

• KUROKAWA Tomohiro

  Research Institute of Innovative Medicine, Tokiwa Foundation Graduate School of Life Science and Engineering, Iryo Sosei University

• SAWATSUBASHI Shun

  Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences/Institute of Biomedical Sciences, Tokushima University

• FUKUMOTO Seiji

  Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences/Institute of Biomedical Sciences, Tokushima University

• MORI Jinichi

  Research Institute of Innovative Medicine, Tokiwa Foundation Graduate School of Life Science and Engineering, Iryo Sosei University Department of Hematology, Jyoban Hospital, Tokiwa Foundation

• KATO Shigeaki

  Research Institute of Innovative Medicine, Tokiwa Foundation Graduate School of Life Science and Engineering, Iryo Sosei University School of Medicine, Fukushima Medical University

抄録

CYP24A1 regulates serum vitamin D (VD) levels by inactivating 25(OH)₂D₃, which is the precursor of the active form of VD [1α,25(OH)₂D₃], and CYP24A1 expression is controlled by multiple calcemic factors such as 1α,25(OH)₂D₃, calcium, and phosphate. A major phosphaturic factor, FGF23, has also been identified as a regulator of serum VD levels by affecting renal CYP24A1 gene expression; however, its effect on CYP24A1 in extrarenal cells remains largely unstudied. Therefore, the direct effect of FGF23 on CYP24A1 was examined in a human keratinocyte cell line (HaCaT). In this cell line, significant induction of CYP24A1 gene expression by 1α,25(OH)₂D₃ was seen within 4 h by qRT-PCR, and this was mediated by the VD receptor, as shown in a mutant cell line genetically deficient in this receptor. However, FGF23 treatment up to 12 h did not induce CYP24A1 expression, although the expected activation of the downstream MAPK signaling pathway was seen. High calcium and phosphate treatments were also ineffective in inducing CYP24A1 gene expression. Furthermore, a luciferase assay showed no activation of a VD-sensitive proximal CYP24A1 promoter in response to the calcium and phosphate treatments, suggesting that the effect of FGF23 on dermal CYP24A1 gene expression is indirect. From these findings, we speculate that CYP24A1 gene regulation by FGF23 occurs mainly in renal cells, but not in extrarenal cells, at least not in keratinocytes.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｎｕｔｒｉｔｉｏｎａｌ　Ｓｃｉｅｎｃｅ　ａｎｄ　Ｖｉｔａｍｉｎｏｌｏｇｙ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｎｕｔｒｉｔｉｏｎａｌ　Ｓｃｉｅｎｃｅ　ａｎｄ　Ｖｉｔａｍｉｎｏｌｏｇｙ 67 (6), 424-428, 2021-12-31

  一般財団法人 学会誌刊行センター

キーワード

• vitamin D
• CYP24A1
• FGF23
• VDR
• transcription

詳細情報

• CRID: 1390009095527259520
• NII論文ID: 130008138260
• NII書誌ID: AA00703822
• DOI: 10.3177/jnsv.67.424
• ISSN: 18817742
• ISSN: 03014800
• NDL書誌ID: 031892071
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I031892071
• Web Site: https://www.jstage.jst.go.jp/article/jnsv/67/6/67_424/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2023054203
• 本文言語コード: en
• データソース種別:
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