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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
Author
Kagawa, Tomohiro University of Tokushima
Kozai, Mina University of Tokushima
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
Yamamoto, Hironori University of Tokushima|Jin-ai University|University of Fukui KAKEN Search Researchers
Keywords
CYP24A1
SREBP1
Thyroid hormone
Transcriptional regulation
Vitamin D
Content Type
Thesis or Dissertation
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.
Journal Title
Biochemical and Biophysical Research Communications
ISSN
0006291X
NCID
AA00564395
AA11542044
Publisher
Elsevier
Volume
500
Issue
2
Start Page
275
End Page
282
Published Date
2018-04-17
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
TextVersion
ETD
MEXT report number
甲第3221号
Diploma Number
甲栄第261号
Granted Date
2018-09-27
Degree Name
Doctor of Nutritional Science
Grantor
Tokushima University
departments
Medical Sciences