ID | 112883 |
Title Alternative | ステロール応答領域結合タンパク質1は腎近位尿細管細胞において25-水酸化ビタミンD3 24-水酸化酵素遺伝子の転写を活性化する
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Author |
Kagawa, Tomohiro
University of Tokushima
Kozai, Mina
University of Tokushima
Masuda, Masashi
University of Tokushima
Tokushima University Educator and Researcher Directory
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Nakahashi, Otoki
Tokushima Bunri University
Tajiri, Mari
University of Tokushima
Yoshikawa, Ryouhei
University of Tokushima
Nakao, Mari
University of Tokushima
Takei, Yuichiro
University of Kochi
Iwano, Masayuki
University of Fukui
Takeda, Eiji
University of Tokushima
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Taketani, Yutaka
University of Tokushima
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Yamamoto, Hironori
University of Tokushima|Jin-ai University|University of Fukui
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Keywords | CYP24A1
SREBP1
Thyroid hormone
Transcriptional regulation
Vitamin D
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Content Type |
Thesis or Dissertation
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Description | The physiological activity of the steroid derived hormone vitamin D is regulated by several enzymatic steps. Both 25-hydroxy vitamin D3 1a-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.
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Journal Title |
Biochemical and Biophysical Research Communications
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ISSN | 0006291X
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NCID | AA00564395
AA11542044
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Publisher | Elsevier
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Volume | 500
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Issue | 2
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Start Page | 275
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End Page | 282
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Published Date | 2018-04-17
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Remark | 内容要旨・審査要旨・論文本文の公開
本論文は, 著者Tomohiro Kagawaの学位論文として提出され, 学位審査・授与の対象となっている。 |
EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第3221号
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Diploma Number | 甲栄第261号
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Granted Date | 2018-09-27
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Degree Name |
Doctor of Nutritional Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
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