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Innovation of novel therapeutics against diabetic nephropathy targeting ChREBP

Research Project

Project/Area Number 16K15492
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Endocrinology
Research InstitutionTohoku University

Principal Investigator

Sugawara Akira  東北大学, 医学系研究科, 教授 (90270834)

Co-Investigator(Renkei-kenkyūsha) SAWATUBASHI Shun  徳島大学, 藤井節郎記念医科学センター, 講師 (70535103)
TAKEMOTO Tatsuya  徳島大学, 藤井節郎記念医科学センター, 助教 (30443899)
YAMAMOTO Yasuhiko  金沢大学, 大学院医歯薬保健学総合研究科, 教授 (20313637)
TAKAGI Kiyoshi  東北大学, 大学院医学系研究科, 助教 (80595562)
Sato Horoshi  東北大学, 大学院薬学研究科, 教授 (60215829)
Yokoyama Atsushi  東北大学, 大学院医学系研究科, 助教 (20572332)
ITO Ryo  東北大学, 大学院医学系研究科, 助教 (80733815)
DOI Takayuki  東北大学, 大学院薬学研究科, 教授 (90212076)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsCRISPR/Cas9システム / ChREBP / 糖尿病性腎症 / ハイスループットスクリーニング / 化合物ライブラリー / 糖質応答転写因子 / 創薬 / スクリーニング
Outline of Final Research Achievements

1) Generation of ChREBP KO mice. We have succeeded in generating ChREBP KO mice (C57BL/6J) using CRISPR/Cas9 system. 2) Generation of high throughput screening (HTS) system using MES13 ChoRE-Luc cells. We have succeeded in generating HTS system using the cell line by obtaining Z score above 0.5. 3) HTS of Tohoku University chemical library: We obtained 13 hit chemicals among 5,861 compounds. Among them, we selected 1 compound (X) for the further investigation. 4) Administration of chemical compounds to Ins-iNOS-transgenic mice: We are now administrating the compound X to the mice.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (10 results)

All 2018 2017 2016 Other

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (5 results) (of which Int'l Joint Research: 5 results) Remarks (1 results)

  • [Journal Article] The reduction of heparan sulphate in the glomerular basement membrane does not augment urinary albumin excretion2018

    • Author(s)
      Satoshi Aoki, Akiko Saito-Hakoda, Takeo Yoshikawa, Kyoko Shimizu, Kiyomi Kisu, Susumu Suzuki, Kiyoshi Takagi, Shuji Mizumoto, Shuhei Yamada, Toin H. van Kuppevelt, Atsushi Yokoyama, Taiji Matsusaka, Hiroshi Sato, Sadayoshi Ito, and Akira Sugawara
    • Journal Title

      Nephrology Dialysis Transplantation

      Volume: 33 Issue: 1 Pages: 26-33

    • DOI

      10.1093/ndt/gfx218

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppressive effects of RXR agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion and blood pressure2017

    • Author(s)
      Suzuki Dai、Saito-Hakoda Akiko、Ito Ryo、Shimizu Kyoko、Parvin Rehana、Shimada Hiroki、Noro Erika、Suzuki Susumu、Fujiwara Ikuma、Kagechika Hiroyuki、Rainey William E.、Kure Shigeo、Ito Sadayoshi、Yokoyama Atsushi、Sugawara Akira
    • Journal Title

      PLoS One

      Volume: 12 Issue: 8 Pages: e0181055-e0181055

    • DOI

      10.1371/journal.pone.0181055

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High glucose stimulates expression of aldosterone synthase (CYP11B2) and secretion of aldosterone in human adrenal cells2017

    • Author(s)
      Shimada Hiroki、Kogure Naotaka、Noro Erika、Kudo Masataka、Sugawara Kaori、Sato Ikuko、Shimizu Kyoko、Kobayashi Makoto、Suzuki Dai、Parvin Rehana、Saito-Ito Takako、Uruno Akira、Saito-Hakoda Akiko、Rainey William E.、Ito Sadayoshi、Yokoyama Atsushi、Sugawara Akira
    • Journal Title

      FEBS Open Bio

      Volume: 7 Issue: 9 Pages: 1410-1421

    • DOI

      10.1002/2211-5463.12277

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of NeuroD1 on the negative regulation of Pomc expression by glucocorticoid.2017

    • Author(s)
      Parvin R, Saito-Hakoda A, Shimada H, Shimizu K, Noro E, Iwasaki Y, Fujiwara K, Yokoyama A, Sugawara A.
    • Journal Title

      PLoS One.

      Volume: 12(4) Issue: 4 Pages: e0175435-e0175435

    • DOI

      10.1371/journal.pone.0175435

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] MEKT1, a novel PPAR-gamma agonist, significantly suppressed Pomc expression/ACTH secretion in AtT20 cells2018

    • Author(s)
      Rehana Parvin, Akiko Saito-Hakoda, Hiroki Shimada, Erika Noro, Susumu Suzuki, Hiroyuki Miyachi Atsushi Yokoyama, Akira Sugawara
    • Organizer
      ENDO2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of IKK complex in the regulation of a glucose-responsive transcriptional factor ChREBP in pancreatic β-cell2018

    • Author(s)
      Erika Noro, Atsushi Yokoyama, Naotaka Kogure, Rina Momma, Kyoko Shimizu, Rehana Parvin, Susumu Suzuki, Hiroki Shimada, Hiroki Shima, Kazuhiko Igarashi, Akira Sugawara
    • Organizer
      ENDO2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Generation and functional analyses of stable H295R cell lines expressing mutants KCNJ5 proteins2018

    • Author(s)
      Ryo Ito, Ikuko Sato, Keita Hoshi, Akira Sugawara
    • Organizer
      ENDO2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Possible Involvement of ChREBP in the Progression of Diabetic Kidney Disease in the Renal Tubules2018

    • Author(s)
      Susumu Suzuki, Atsushi Yokoyama, Erika Noro, Satoshi Aoki, Rehana Parvin, Hiroki Shimada, Akira Sugawara
    • Organizer
      ISN Frontiers Meeting 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional screening of transcriptional co-factors for a glucose-responsive transcriptional factor ChREBP.2016

    • Author(s)
      Erika Noro, Atsushi Yokoyama, Naotaka Kogure, Kyoko Shimizu, Hiroki Shima, Kazuhiko Igarashi, Akira Sugawara
    • Organizer
      ENDO2016
    • Place of Presentation
      アメリカ合衆国ボストン市
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 東北大学大学院医学系研究科・分子内分泌学分野

    • URL

      http://www.med.tohoku.ac.jp/about/laboratory/189.html

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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