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

• Material Type: 博士論文
• Title: Sterol regulatory element binding protein 1 trans-activates 25-hydroxy vitamin D3 24-hydroxylase gene expression in renal proximal tubular cells
• Author/Editor: Kagawa, Tomohiro; Kozai, Mina; Masuda, Masashi; Harada, Nagakatsu; Nakahashi, Otoki; Tajiri, Mari; Yoshikawa, Ryouhei; Nakao, Mari; Takei, Yuichiro; Iwano, Masayuki; Takeda, Eiji; Taketani, Yutaka; Yamamoto, Hironori
• Author Heading: Kagawa, Tomohiro; Kozai, Mina; Masuda, Masashi; Harada, Nagakatsu; Nakahashi, Otoki; Tajiri, Mari; Yoshikawa, Ryouhei; Nakao, Mari; Takei, Yuichiro; Iwano, Masayuki; Takeda, Eiji; Taketani, Yutaka; Yamamoto, Hironori
• Publication, Distribution, etc.: Elsevier
• Publication Date: 2018-04-17
• Publication Date (W3CDTF): 2018-04-17
• Alternative Title: 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
• Periodical title: Biochemical and Biophysical Research Communications
• No. or year of volume/issue: 500 2
• Volume: 500
• Issue: 2
• Pages: 275-282
• ISSN (Periodical Title): ISSN : 0006-291X
• Degree grantor/type: 徳島大学
• Date Granted: 2018-09-27
• Dissertation Number: 甲第3221号
• Degree Type: 博士（栄養学）
• Text Language Code: eng
• Subject Heading: CYP24A1; SREBP1; Thyroid hormone; Transcriptional regulation; Vitamin D
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1016/j.bbrc.2018.04.058
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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https://repo.lib.tokushima-u.ac.jp/files/public/11/112883/20181218160133499275/k3221_abstract_review.pdf fulltext

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