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Homeostatic Response of Mouse renin Gene Transcription in a Hypertensive Environment Is Mediated by a Novel 5′ Enhancer
http://hdl.handle.net/2241/00151513
http://hdl.handle.net/2241/001515135857bdca-0c1c-4178-b28a-9d3573c4219d
名前 / ファイル | ライセンス | アクション |
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MCB_38-7 (2.5 MB)
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Item type | Journal Article(1) | |||||
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公開日 | 2018-04-26 | |||||
タイトル | ||||||
タイトル | Homeostatic Response of Mouse renin Gene Transcription in a Hypertensive Environment Is Mediated by a Novel 5′ Enhancer | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Ushiki, Aki
× Ushiki, Aki× Matsuzaki, Hitomi× Fukamizu, Akiyoshi× Tanimoto, Keiji |
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著者別名 |
谷本, 啓司
× 谷本, 啓司× 深水, 昭吉× 松﨑, 仁美 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The renin-angiotensin system plays an essential role in blood pressure homeostasis. Because renin activity is reflected as a blood pressure phenotype, its gene expression in the kidney is tightly regulated by a feedback mechanism; i.e., renin gene transcription is suppressed in a hypertensive state. To address the molecular mechanisms controlling hypertension-responsive mouse renin (mRen) gene regulation, we deleted either 5′ (17-kb) or 3′ (78-kb) regions of the endogenous mRen gene and placed the animals in a hypertensive environment. While the mRen gene bearing the 3′ deletion was appropriately downregulated, the one bearing the 5′ deletion lost this hypertension responsiveness. Because the 17-kb sequence exhibited enhancer activity in vivo and in vitro, we narrowed down the enhancer to a 2.3-kb core using luciferase assays in As4.1 cells. When this 2.3-kb sequence was removed from the endogenous mRen gene in the mouse, its basal expression was dramatically reduced, and the hypertension responsiveness was significantly attenuated. Furthermore, we demonstrated that the angiotensin II signal played an important role in mRen gene suppression. We propose that in a hypertensive environment, the activity of this novel enhancer is attenuated, and, as a consequence, mRen gene transcription is suppressed to maintain blood pressure. | |||||
書誌情報 |
Molecular and cellular biology 巻 38, 号 7, p. e00566-17, 発行日 2018-04 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0270-7306 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10620925 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 29358217 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1128/MCB.00566-17 | |||||
権利 | ||||||
権利情報 | © 2018 American Society for Microbiology. | |||||
著者版フラグ | ||||||
値 | publisher | |||||
出版者 | ||||||
出版者 | American Society for Microbiology |