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

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)

Author
著者 王 娟
著者(ヨミ) ワン ジュアン
著者(別表記) Wang Juan
Publication Title
PLoS ONE
Publication Title Alternative
PLoS One.
Volume
12
Issue
10
Start Page
e0185600
End Page
e0185600
Publisher
Public Library of Science
Published Date
2017-10-20
ISSN
1932-6203
PMID
29053707
DOI
10.1371/journal.pone.0185600
Resource Type
Thesis or Dissertation
Language
eng
Relation
出版社版DOIリンク(URL): https://doi.org/10.1371/journal.pone.0185600
PMCID: PMC5650141
Resource URL
https://doi.org/10.1371/journal.pone.0185600
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650141/
Rights
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
Text Version
ETD
Grant ID
博甲第685号
Grant Date
2018-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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