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High glucose augments angiotensinogen in human renal proximal tubular cells through hepatocyte nuclear factor-5
https://kagawa-u.repo.nii.ac.jp/records/305
https://kagawa-u.repo.nii.ac.jp/records/305951f1603-12a3-4f30-87c1-6245f3d34ba4
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本文 (834.9 kB)
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内容の要旨 (76.5 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||||
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| 公開日 | 2018-06-01 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | High glucose augments angiotensinogen in human renal proximal tubular cells through hepatocyte nuclear factor-5 | |||||||||||||
| 言語 | en | |||||||||||||
| 言語 | ||||||||||||||
| 言語 | eng | |||||||||||||
| 資源タイプ | ||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||||
| 資源タイプ | doctoral thesis | |||||||||||||
| アクセス権 | ||||||||||||||
| アクセス権 | open access | |||||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||||
| 著者 |
王, 娟
× 王, 娟
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | High glucose has been demonstrated to induce angiotensinogen (AGT) synthesis in the renal proximal tubular cells (RPTCs) of rats, which may further activate the intrarenal renin-angiotensin system (RAS) and contribute to diabetic nephropathy. This study aimed to investigate the effects of high glucose on AGT in the RPTCs of human origin and identify the glucose-responsive transcriptional factor(s) that bind(s) to the DNA sequences of AGT promoter in human RPTCs. Human kidney (HK)-2 cells were treated with normal glucose (5.5 mM) and high glucose (15.0 mM), respectively. Levels of AGT mRNA and AGT secretion of HK-2 cells were measured by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Consecutive 5’-end deletion mutant constructs and different site-directed mutagenesis products of human AGT promoter sequences were respectively transfected into HK-2 cells, followed by AGT promoter activity measurement through dual luciferase assay. High glucose significantly augmented the levels of AGT mRNA and AGT secretion of HK-2 cells, compared with normal glucose treatment. High glucose also significantly augmented AGT promoter activity in HK-2 cells transfected with the constructs of human AGT promoter sequences, compared with normal glucose treatment. Hepatocyte nuclear factor (HNF)-5 was found to be one of the glucose-responsive transcriptional factors of AGT in human RPTCs, since the mutation of its binding sites within AGT promoter sequences abolished the above effects of high glucose on AGT promoter activity as well as levels of AGT mRNA and its secretion. The present study has demonstrated, for the first time, that high glucose augments AGT in human RPTCs through HNF-5, which provides a potential therapeutic target for diabetic nephropathy. | |||||||||||||
| 言語 | en | |||||||||||||
| 学位名 | ||||||||||||||
| 言語 | ja | |||||||||||||
| 学位名 | 博士（医学） | |||||||||||||
| 学位授与機関 | ||||||||||||||
| 識別子Scheme | kakenhi | |||||||||||||
| 識別子 | 16201 | |||||||||||||
| 言語 | ja | |||||||||||||
| 機関名 | 香川大学 | |||||||||||||
| 言語 | en | |||||||||||||
| 機関名 | Kagawa University | |||||||||||||
| 学位授与年月日 | ||||||||||||||
| 学位授与年月日 | 2018-03-24 | |||||||||||||
| 学位授与番号 | ||||||||||||||
| 学位授与番号 | 甲第685号 | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報 | Copyright: © 2017 Wang et al. | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報Resource | https://creativecommons.org/licenses/by/4.0/ | |||||||||||||
| 権利情報 | This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | |||||||||||||
| 論文ID（NAID） | ||||||||||||||
| 識別子タイプ | NAID | |||||||||||||
| 関連識別子 | 500001069856 | |||||||||||||
| PubMed番号 | ||||||||||||||
| 識別子タイプ | PMID | |||||||||||||
| 関連識別子 | 29053707 | |||||||||||||
| 関連サイト | ||||||||||||||
| 関連タイプ | isVersionOf | |||||||||||||
| 識別子タイプ | DOI | |||||||||||||
| 関連識別子 | https://doi.org/10.1371/journal.pone.0185600 | |||||||||||||
| 関連サイト | ||||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||||
| 識別子タイプ | URI | |||||||||||||
| 関連識別子 | https://dl.ndl.go.jp/pid/11122662 | |||||||||||||
| 関連サイト | ||||||||||||||
| 関連タイプ | hasVersion | |||||||||||||
| 識別子タイプ | URI | |||||||||||||
| 関連識別子 | http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5650141/ | |||||||||||||
| 助成情報 | ||||||||||||||
| 識別子タイプ | Crossref Funder | |||||||||||||
| 助成機関識別子 | https://doi.org/10.13039/501100001691 | |||||||||||||
| 助成機関名 | 日本学術振興会 | |||||||||||||
| 言語 | ja | |||||||||||||
| 助成機関名 | Japan Society for the Promotion of Science | |||||||||||||
| 言語 | ja | |||||||||||||
| 研究課題番号URI | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26460343/ | |||||||||||||
| 研究課題番号 | 26460343 | |||||||||||||
| 研究課題名 | 交感神経と局所RAASをターゲットとした脳心腎・糖代謝連関に対する治療法の開発 | |||||||||||||
| 言語 | ja | |||||||||||||
| 研究課題名 | New therapeutic strategy for brain-cardiorenal-glucose metabolism syndrome: targeting on the sympathetic nervous system and SGLT2 | |||||||||||||
| 言語 | en | |||||||||||||
| 著者版フラグ | ||||||||||||||
| 出版タイプ | P | |||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||||||||||
| KEID | ||||||||||||||
| 28455 | ||||||||||||||
