論文

査読有り
2018年6月2日

Sterol regulatory element binding protein 1 trans-activates 25-hydroxy vitamin D3 24-hydroxylase gene expression in renal proximal tubular cells

Biochemical and Biophysical Research Communications
  • Tomohiro Kagawa
  • ,
  • Mina Kozai
  • ,
  • Masashi Masuda
  • ,
  • Nagakatsu Harada
  • ,
  • Otoki Nakahashi
  • ,
  • Mari Tajiri
  • ,
  • Ryouhei Yoshikawa
  • ,
  • Mari Nakao
  • ,
  • Yuichiro Takei
  • ,
  • Masayuki Iwano
  • ,
  • Eiji Takeda
  • ,
  • Yutaka Taketani
  • ,
  • Hironori Yamamoto

500
2
開始ページ
275
終了ページ
282
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2018.04.058
出版者・発行元
Elsevier B.V.

The physiological activity of the steroid derived hormone vitamin D is regulated by several enzymatic steps. Both 25-hydroxy vitamin D3 1α-hydroxylase (CYP27B1) and 25-hydroxyvitamin D3 24-hydroxylase (CYP24A1) modulate blood levels of 1,25-dihydroxyvitamin D3, an activated form of vitamin D. We previously demonstrated that CYP27B1 expression was trans-activated by sterol regulatory element binding protein 1 (SREBP1), although whether SREBP1 also regulates CYP24A1 transcription was unclear. Here we investigated the ability of SREBP1 to affect CYP24A1 transcription. In a luciferase reporter assay, mouse and human CYP24A1 promoter activity was strongly activated by SREBP1 in opossum kidney proximal tubular cells (OK-P). Three putative SREs (pSREs) were found in the mouse Cyp24a1 gene promoter and the SREBP1 protein showed specific binding to the pSRE1 element in EMSAs. Site-directed mutagenesis of the pSRE1 element strongly decreased SREBP1-mediated Cyp24a1 gene transcription. Moreover, siRNA-mediated SREBP1 knock-down repressed CYP24A1 expression in human renal proximal tubular epithelial cells (HKC-8). In animal studies, mice given various doses of thyroid hormone (T3) showed dose-dependent reductions in renal Srebp1c and Cyp24a1 mRNA levels. Taken together, our results suggest that SREBP1 trans-activates CYP24A1 expression through SREBP binding elements present in the promoter.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2018.04.058
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29653103
ID情報
  • DOI : 10.1016/j.bbrc.2018.04.058
  • ISSN : 1090-2104
  • ISSN : 0006-291X
  • PubMed ID : 29653103
  • SCOPUS ID : 85045429371

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