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Screening of drug target proteins for diabetic nephropathy by identification of ChREBP complex from renal mesangial cells

Research Project

Project/Area Number 16K08606
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionTohoku University

Principal Investigator

Yokoyama Atsushi  東北大学, 医学系研究科, 助教 (20572332)

Research Collaborator SHIMA hiroki  
SUGAWARA akira  
NORO erika  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords生化学 / 糖尿病 / 腎症 / 糖尿病性腎症 / ChREBP / メサンギウム細胞 / 炎症 / RIME / 代謝異常学 / 遺伝子発現制御
Outline of Final Research Achievements

In this research projecct, we focused on ChREBP, a DNA-binding transcription factor which is believed to be involved in diabetic nephropathy pathogenesis. To understand ChREBP-mediated transcriptional regulation, we tried to identify ChREBP-containing protein complex using renal mesangial cells. In this attempt, we identified several coregulator candidates for ChREBP and, we also identified cross-talk mechanisms between ChREBP and inflammation signals. To developing drugs targeting these factors might be promising strategy for diabetic nephropathy and other metabolic syndromes.

Academic Significance and Societal Importance of the Research Achievements

本研究課題においては、糖尿病性腎症の発症に関わると考えられているChREBPという転写因子に着目しその転写活性を制御するメカニズムの解明を行った。その結果、転写制御に関わると考えられる候補因子を複数見出すことができた。これらの因子の解析と、これらを標的とした薬剤の開発は糖尿病性腎症をはじめとした生活習慣病の治療薬の開発へと繋がる可能性がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(20 results)

All 2019 2018 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Transglutaminase-mediated cross-linking of WDR54 regulates EGF receptor-signaling.2019

    • Author(s)
      Maeda A. Nishino T, Matsuzaki R, Yokoyama A, Suga H, Yagi T, Konishi H.
    • Journal Title

      Biochim Biophys Acta Mol Cell Res.

      Volume: 1866 Pages: 285-295

    • DOI

      10.1016/j.bbamcr.2018.11.009

    • Description
      [Epub ahead of print]
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Partial proteasomal degradation of Lola triggers the male-to-female switch of a dimorphic courtship circuit.2019

    • Author(s)
      Kosei Sato, Hiroki Ito, Atsushi Yokoyama, Gakuta Toba and Daisuke Yamamoto
    • Journal Title

      Nat Commun

      Volume: 10 Pages: 166-166

    • DOI

      10.1038/s41467-018-08146-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells.2018

    • Author(s)
      Parvin R, Noro E, Saito-Hakoda A, Shimada H, Suzuki S, Shimizu K, Miyachi H, Yokoyama A, Sugawara A
    • Journal Title

      PPAR Res

      Volume: 2018 Pages: 1-16

    • DOI

      10.1155/2018/5346272

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endogenous Purification of NR4A2 (Nurr1) Identified Poly(ADP-Ribose) Polymerase 1 as a Prime Coregulator in Human Adrenocortical H295R Cells.2018

    • Author(s)
      Noro, E., Yokoyama, A., Kobayashi, M., Shimada, H., Suzuki, S., Hosokawa, M., Takehara, T., Parvin, R., Shima, H., Igarashi, K. and Sugawara A.
    • Journal Title

      Int J Mol Sci

      Volume: 19 Pages: 1406-1406

    • DOI

      10.3390/ijms19051406

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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

      Nephrol. Dial. Transplant.

      Volume: 33 Pages: 26-33

    • DOI

      10.1093/ndt/gfx218

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibitory effects of a novel PPAR-gamma agonist MEKT1 on Pomc expression/ACTH secretion in AtT20 cells2018

    • Author(s)
      Parvin R, Noro E, Saito-Hakoda A, Shimada H, Suzuki S, Shimizu K, Miyachi H, Yokoyama A, Sugawara A.
    • Journal Title

      PPAR Res

      Volume: 2018 Pages: 1-16

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A ubiquitin-proteasome inhibitor bortezomib suppresses the expression of CYP11B2, a key enzyme of aldosterone synthesis2017

    • Author(s)
      Ito Ryo、Sato Ikuko、Tsujita Tadayuki、Yokoyama Atsushi、Sugawara Akira
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 489 Pages: 21-28

    • DOI

      10.1016/j.bbrc.2017.05.109

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Pages: 1410-1421

    • DOI

      10.1002/2211-5463.12277

    • Related Report
      2017 Research-status 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

    • DOI

      10.1371/journal.pone.0181055

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biochemical Analysis of Histone Succinylation2017

    • Author(s)
      Yokoyama Atsushi、Katsura Shogo、Sugawara Akira
    • Journal Title

      Biochem Res Int

      Volume: 2017 Pages: 1-7

    • DOI

      10.1155/2017/8529404

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2)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, Fujii K, Yokoyama A, Sugawara A.
    • Journal Title

      PLoS One

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Identification of novel AR coregulators via endogenous purification2018

    • Author(s)
      Atsushi Yokoyama, Erika Noro, Makoto Kobayashi, Kyoko Shimizu, Susumu Suzuki, Hiroki Shimada, Hiroki Shima, Kazuhiko Igarashi, Akira Sugawara
    • Organizer
      ENDO 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 前立腺癌細胞を用いたアンドロゲン受容体の新たな転写共役因子の探索2018

    • Author(s)
      横山 敦,菅原 明
    • Organizer
      第36回内分泌代謝学サマーセミナー
    • Related Report
      2018 Annual Research Report
  • [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
      ENDO 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 膵β細胞におけるグルコース応答性転写因子ChREBPの機能制御因子のRIME法を用いた探索2018

    • Author(s)
      野呂英理香 、横山敦、小暮直敬、鈴木歩、清水恭子、島弘季、五十嵐和彦、菅原明
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification of novel AR coregulators via endogenous purification2018

    • Author(s)
      Atsushi Yokoyama, Erika Noro, Makoto Kobayashi, Kyoko Shimizu, Susumu Suzuki, Hiroki Shimada, Hiroki Shima, Kazuhiko Igarashi, Akira Sugawara
    • Organizer
      the 100th Annual Meeting of the Endocrine Society ENDO 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 核内受容体の新たな転写制御因子の探索2017

    • Author(s)
      野呂英理香、小林真、清水恭子、鈴木歩、島弘季、五十嵐和彦、菅原明
    • Organizer
      第2回次世代生命科学の研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新たな翻訳後修飾の探索2016

    • Author(s)
      横山敦、菅原明
    • Organizer
      第89会生化学会大会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 新たな転写複合体同定の試み2016

    • Author(s)
      横山敦
    • Organizer
      第1回次世代生命科学の研究会
    • Place of Presentation
      徳島大学(徳島県蔵本町)
    • Year and Date
      2016-08-12
    • Related Report
      2016 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 1,3ージオキソラン誘導体2019

    • Inventor(s)
      菅原明、横山敦、鈴木歩、岩渕好治、土井隆行
    • Industrial Property Rights Holder
      菅原明、横山敦、鈴木歩、岩渕好治、土井隆行
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-025963
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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