High glucose augments angiotensinogen in human renal proximal tubular cells through hepatocyte nuclear factor-5

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/28455
タイトル
High glucose augments angiotensinogen in human renal proximal tubular cells through hepatocyte nuclear factor-5
ファイル
内容記述

Abstract

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 nephropath

(医博甲685)

著者
著者 王 娟
著者(ヨミ) ワン ジュアン
著者(別表記) Wang Juan
掲載誌
PLoS ONE
掲載誌(別表記)
PLoS One.
12
10
開始ページ
e0185600
終了ページ
e0185600
出版者
Public Library of Science
出版年月日
2017-10-20
ISSN
1932-6203
PMID
29053707
DOI
10.1371/journal.pone.0185600
資料タイプ
学位論文
言語
英語
関連情報
出版社版DOIリンク(URL): https://doi.org/10.1371/journal.pone.0185600
PMCID: PMC5650141
関連情報URL
https://doi.org/10.1371/journal.pone.0185600
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650141/
権利関係
出版社の著作権ポリシーにより、論文の本文は、「クリエイティブ・コモンズ 表示 4.0 国際 ライセンス」(CC-BY 4.0)で提供されます。 / Depending on the copyright policy of the publisher, the body of the paper is provided in Creative Commons Attribution 4.0 international license (CC-BY 4.0).
著者は著作権を保持します。 / Authors retain copyright
Copyright © 2017 Wang et al
DOI: https://doi.org/10.1371/journal.pone.0185600
博士論文(全文を含む)
学位授与番号
博甲第685号
学位授与年月日
2018-03-24
学位名
博士(医学)
学位授与機関
香川大学
区分
香川大学
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