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An approach to identify novel therapeutics against diabetic nephropathy based on aldosterone synthase gene regulation

Research Project

Project/Area Number 25461381
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionTohoku University

Principal Investigator

Sugawara Akira  東北大学, 医学(系)研究科(研究院), 教授 (90270834)

Co-Investigator(Renkei-kenkyūsha) ITO TAKAKO (SAITO TAKAKO)  東北大学, 病院, 助教 (10375173)
KUDO MASATAKA  東北大学, 病院, 准教授 (20509583)
HAKODA AKIKO (SAITO AKIKO)  JR仙台病院, 小児科, 医長 (70509398)
MATSUDA KEN  石巻赤十字病院, 内科, 副部長 (60645935)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsアルドステロン / 糖尿病 / 高血圧 / CYP11B2 / 遺伝子改変マウス / DNAマイクロアレイ / 糖尿病性腎症 / 創薬
Outline of Final Research Achievements

We here have first demonstrated that high glucose (D-glucose) stimulates aldosterone synthase (CYP11B2) gene transcription and mRNA expression via the induction of transcription factor Nurr-1, and results in the increase of aldosterone secretion using human adrenocortical H295R cells. It is therefore suggested that high glucose levels in diabetic patients may promote hypertension, atherosclerosis, and diabetic nephropathy via the induction of aldosterone secretion.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (20 results)

All 2016 2015 2014 Other

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results) Book (2 results) Remarks (4 results)

  • [Journal Article] Hydroxylation of methylated DNA by TET1 in chondrocyte differentiation of C3H10T1/2 cells2016

    • Author(s)
      Ito R, Shimada H, Yazawa K, Sato I, Imai Y, Sugawara A, Yokoyama A
    • Journal Title

      Biochem Biophys Rep

      Volume: 5 Pages: 134-140

    • DOI

      10.1016/j.bbrep.2015.11.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The roles of histone modifier complexes in tissue-specific transcriptional regulation2015

    • Author(s)
      横山 敦、菅原 明
    • Journal Title

      生化学

      Volume: 87 Issue: 5 Pages: 621-624

    • DOI

      10.14952/SEIKAGAKU.2015.870621

    • NAID

      40020650274

    • ISSN
      0037-1017
    • Year and Date
      2015-10-25
    • Related Report
      2015 Annual Research Report
  • [Journal Article] Role of Histamine H3 Receptor in Glucagon-Secreting αTC1.6 cells2015

    • Author(s)
      Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Attyeb Mohsen, Tomomitsu iida, Yamato Miura, Akira Sugawara and Kazuhiko Yanai
    • Journal Title

      FEBS Open Bio

      Volume: 5 Issue: 1 Pages: 36-41

    • DOI

      10.1016/j.fob.2014.12.001

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effects of RXR agonists on cell proliferation/apoptosis and ACTH secretion/Pomc expression2015

    • Author(s)
      Saito-Hakoda A, Uruno A, Yokoyama A, Shimizu K, Parvin R, Kudo M, Saito-Ito T, Sato I, Kogure N, Suzuki D, Shimada H, Yoshikawa T, Fujiwara I, Kagechika H, Iwasaki Y, Kure S, Ito S, Sugawara A
    • Journal Title

      PLoS One

      Volume: 10 Issue: 12 Pages: e0141960-e0141960

    • DOI

      10.1371/journal.pone.0141960

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Retinoic acid receptor-α up-regulates proopiomelanocortin gene expression in AtT20 corticotroph cells.2014

    • Author(s)
      Uruno A, Saito-Hakoda A, Yokoyama A, Kogure N, Matsuda K, Parvin R, Shimizu K, Sato I, Kudo M, Yoshikawa T, Kagechika H, Iwasaki Y, Ito S, Sugawara A.
    • Journal Title

      Endocr J.

      Volume: 61 Pages: 1105-1114

    • NAID

      130004677954

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex.2014

    • Author(s)
      Yokoyama A, Igarashi K, Sato T, Takagi K, Otsuka I M, Shishido Y, Baba T, Ito R, Kanno J, Ohkawa Y, Morohashi K, Sugawara A.
    • Journal Title

      J Biol Chem.

      Volume: 289 Issue: 26 Pages: 18152-18162

    • DOI

      10.1074/jbc.m114.566448

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA).2014

    • Author(s)
      Nakamura Y, Hattangady NG, Ye P, Satoh F, Morimoto R, Ito-Saito T, Sugawara A, Ohba K, Takahashi K, Rainey WE, Sasano H.
    • Journal Title

      Mol Cell Endocrinol.

      Volume: 384 Issue: 1-2 Pages: 102-108

    • DOI

      10.1016/j.mce.2014.01.016

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues.2014

    • Author(s)
      Felizola SJ, Nakamura Y, Ono Y, Kitamura K, Kikuchi K, Onodera Y, Ise K, Takase K, Sugawara A, Hattangady N, Rainey WE, Satoh F, Sasano H.
    • Journal Title

      J Mol Endocrinol.

      Volume: 52 Issue: 2 Pages: 159-167

    • DOI

      10.1530/jme-13-0248

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells.2014

    • Author(s)
      Matsuda K, Uruno A, Kogure N, Sugawara K, Shimada H, Nezu M, Saito-Ito T, Iki Y, Kudo M, Shimizu K, Sato I, Yoshikawa T, Satoh F, Ito R, Yokoyama A, Rainey WE, Saito-Hakoda A, Ito S, Sugawara A.
    • Journal Title

      Mol Cell Endocrinol.

      Volume: 383(1-2) Issue: 1-2 Pages: 60-68

    • DOI

      10.1016/j.mce.2013.12.004

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Presentation] An approach to identify the undetermined adipocyte-derived factor(s) that stimulate aldosterone synthase gene (CYP11B2) expression2016

    • Author(s)
      Shimada H, Ito R, Sato I, Sato E, Yokoyama A, Sugawara A
    • Organizer
      41st International Aldosterone Conference
    • Place of Presentation
      アメリカ合衆国ボストン市
    • Year and Date
      2016-03-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Suppressive effects of retinoid X receptor (RXR) agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion, and blood pressure2016

    • Author(s)
      Suzuki D, Saito-Hakoda A, Ito R, Shimizu K, Kogure N, Kagechika H, Kure S, Yokoyama A, Sugawara A
    • Organizer
      41st International Aldosterone Conference
    • Place of Presentation
      アメリカ合衆国ボストン市
    • Year and Date
      2016-03-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] High-glucose stimulates aldosterone synthase gene (CYP11B2) expression via the induction of T-type calcium channels in H295R cells2014

    • Author(s)
      Naotaka Kogure, Ken Matsuda, Akira Uruno, Kaori Sugawara, Ikuko Sato, Kyoko Shimizu, Rehana Parvin, Takeo Yoshikawa Masataka Kudo, Akiko Saito-Hakoda, Ryo Ito, Atsushi Yokoyama, Sadayoshi Ito, Akira Sugawara
    • Organizer
      ICE/ENDO2014
    • Place of Presentation
      アメリカ合衆国シカゴ
    • Year and Date
      2014-06-23
    • Related Report
      2014 Research-status Report 2013 Research-status Report
  • [Presentation] The innovation of a novel drug screening system for the inhibitors of aldosterone synthase gene (CYP11B2) expression2014

    • Author(s)
      Ryo Ito, Ken Matsuda, Akira Uruno, Atsushi Yokoyama, Akira Sugawara
    • Organizer
      ICE/ENDO2014
    • Place of Presentation
      アメリカ合衆国シカゴ
    • Year and Date
      2014-06-23
    • Related Report
      2014 Research-status Report 2013 Research-status Report
  • [Presentation] Generation of a stable H295R cell line expressing 11-hydroxylase gene promoter and the effect of high-glucose on its expression2014

    • Author(s)
      Kaori Sugawara, Ken Matsuda, Naotaka Kogure, Akira Uruno, Ikuko Sato, Kyoko Shimizu, Rehana Parvin, Takeo Yoshikawa Masataka Kudo, Akiko Saito-Hakoda, Ryo Ito, Atsushi Yokoyama, Sadayoshi Ito, Akira Sugawara
    • Organizer
      ICE/ENDO2014
    • Place of Presentation
      アメリカ合衆国シカゴ
    • Year and Date
      2014-06-21
    • Related Report
      2014 Research-status Report
  • [Book] 今日の診断指針(第7版)2015

    • Author(s)
      菅原 明
    • Total Pages
      2103
    • Publisher
      医学書院
    • Related Report
      2015 Annual Research Report
  • [Book] 南山堂医学大辞典(改訂20版)2015

    • Author(s)
      菅原 明
    • Total Pages
      3101
    • Publisher
      南山堂
    • Related Report
      2015 Annual Research Report
  • [Remarks] 分子内分泌学分野

    • URL

      http://www.med.tohoku.ac.jp/org/health/84/index.html

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Remarks] Molecular Endocrinology

    • URL

      http://www.med.tohoku.ac.jp/english/org/health/84/index.html

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Remarks] 分子内分泌学分野

    • URL

      http://www.med.tohoku.ac.jp/org/health/84/index.html

    • Related Report
      2013 Research-status Report
  • [Remarks] Molecular Endocrinology

    • URL

      http://www.med.tohoku.ac.jp/english/org/health/84/index.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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