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Vaspin inhibits tubulointerstitial injury via maintaining mitochondrial homeostasis

Research Project

Project/Area Number 20K08608
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionOkayama University

Principal Investigator

Nakatsuka Atsuko  岡山大学, 大学病院, 講師 (00625949)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsアディポカイン / Vaspin / ミトコンドリア / 糖尿病腎症 / 尿細管間質障害
Outline of Research at the Start

これまでに、我々が発見した生理活性物質バスピンが近位尿細管細胞の保護作用を有する見出した。また、機能が十分解明されていない分子HSPA1L (heat shock protein 70kDa-1 like)を介してバスピンが作用することを発見し、HSPA1Lに注目した。
本研究では、HSPA1Lがミトコンドリアやリソソームの機能を維持し、近位尿細管細胞を保護すること、またHSPA1Lの細胞外での新規機能について明らかにする。そしてバスピンのHSPA1Lを介した作用分子機序を解明する。本研究により、腎予後に強く関係する尿細管間質障害の病態解明や新たなバイオマーカー、治療法の発見に繋げたい。

Outline of Final Research Achievements

Tubular interstitial injury is a major risk for renal dysfunction. Tubular cells have high energy demands due to their multifunctional cellularity, and mitochondria are among the most abundant cells, so it is important to maintain mitochondrial function. In this study, we show that Vaspin, secreted by adipocytes, reaches the kidney via the blood and maintains mitochondrial function via HSPA1L, reducing tubulointerstitial damage in diabetic nephropathy.

Academic Significance and Societal Importance of the Research Achievements

バスピンのミトコンドリア恒常性維持における意義を解明することは、今後、腎臓以外にも、心臓や褐色脂肪など、ミトコンドリアが豊富な臓器や細胞に関する病態の解明や、疾患治療への応用が可能と考えられる。
また、これまで十分機能が解明されていないHSPA1Lの機能を明らかにすることは、学術的な今後の研究の広がりにつながる。

Report

(3 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (4 results) Book (1 results)

  • [Journal Article] Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4.2022

    • Author(s)
      Yamaguchi S, Zhang D, Katayama A, Kurooka N, Sugawara R, Albuayjan HHH, Nakatsuka A, Eguchi J, Wada J.
    • Journal Title

      Front Endocrinol (Lausanne).

      Volume: 12 Pages: 750261-750261

    • DOI

      10.3389/fendo.2021.750261

    • NAID

      120007188342

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study.2022

    • Author(s)
      Kurooka N, Eguchi J, Murakami K, Kamei S, Kikutsuji T, Sasaki S, Seki A, Yamaguchi S, Nojima I, Watanabe M, Higuchi C, Katayama A, Uchida HA, Nakatsuka A, Shikata K, Wada J.
    • Journal Title

      J Clin Lipidol.

      Volume: 22 Issue: 2 Pages: 21-26

    • DOI

      10.1016/j.jacl.2022.01.006

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Current Status of Familial LCAT Deficiency in Japan2021

    • Author(s)
      Kuroda Masayuki、Bujo Hideaki、Yokote Koutaro、Murano Takeyoshi、Yamaguchi Takashi、Ogura Masatsune、Ikewaki Katsunori、Koseki Masahiro、Takeuchi Yasuo、Nakatsuka Atsuko、Hori Mika、Matsuki Kota、Miida Takashi、Yokoyama Shinji、Wada Jun、Harada-Shiba Mariko.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 28 Issue: 7 Pages: 679-691

    • DOI

      10.5551/jat.RV17051

    • NAID

      130008060155

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2021-07-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2).2021

    • Author(s)
      Mise K, Imamura M, Yamaguchi S, Watanabe M, Higuchi C, Katayama A, Miyamoto S, Uchida HA, Nakatsuka A, Eguchi J, Hida K, Nakato T, Tone A, Teshigawara S, Matsuoka T, Kamei S, Murakami K, Shimizu I, Miyashita K, Ando S, Nunoue T, Yoshida M, Yamada M, Shikata K, Wada J.
    • Journal Title

      Front Cardiovasc Med.

      Volume: 8 Pages: 668059-668059

    • DOI

      10.3389/fcvm.2021.668059

    • NAID

      120007053373

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Upregulation of Mir342 in Diet-Induced Obesity Mouse and the Hypothalamic Appetite Control.2021

    • Author(s)
      Zhang D, Yamaguchi S, Zhang X, Yang B, Kurooka N, Sugawara R, Albuayjan HHH, Nakatsuka A, Eguchi J, Hiyama TY, Kamiya A, Wada J.
    • Journal Title

      Front Endocrinol (Lausanne).

      Volume: 12 Pages: 727915-727915

    • DOI

      10.3389/fendo.2021.727915

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease2021

    • Author(s)
      Nakatsuka A, Yamaguchi S, Eguchi J, Kakuta S, Iwakura Y, Sugiyama H, Wada J.
    • Journal Title

      Commun Biol .

      Volume: 4 Issue: 1 Pages: 373-373

    • DOI

      10.1038/s42003-021-01902-y

    • NAID

      120007004153

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2.2021

    • Author(s)
      Nunoue T, Yamaguchi S, Teshigawara S, Katayama A, Nakatsuka A, Eguchi J, Niki T, Wada J.
    • Journal Title

      Sci Rep.

      Volume: 16 Issue: 1 Pages: 5991-5991

    • DOI

      10.1038/s41598-021-85080-1

    • NAID

      120007004155

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysfunction of CD8 + PD-1 + T cells in type 2 diabetes caused by the impairment of metabolism-immune axis2020

    • Author(s)
      Nojima I, Eikawa S, Tomonobu N, Hada Y, Kajitani N, Teshigawara S, Miyamoto S, Tone A, Uchida HA, Nakatsuka A, Eguchi J, Shikata K, Udono H, Wada J.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 14928-14928

    • DOI

      10.1038/s41598-020-71946-3

    • NAID

      120006891215

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 臨床医・研究者として継続してきたVaspinの機能解析 (会長企画ー研究者のサークルを作ろうー3 女性、連携、新しい糖尿病学を切り拓く)2022

    • Author(s)
      中司敦子
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 糖尿病合併症におけるバスピンの作用と新たな病態解明2022

    • Author(s)
      中司敦子
    • Organizer
      第64回日本糖尿病学会年次学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 基礎研究と臨床の間で考える糖尿病合併症2022

    • Author(s)
      中司敦子
    • Organizer
      日本糖尿病学会中国四国地方会第59回総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 糖尿病における近位尿細管障害とVaspin/HSP70sの意義2022

    • Author(s)
      中司敦子、和田淳
    • Organizer
      第32回日本糖尿病性腎症研究会
    • Related Report
      2021 Research-status Report
  • [Book] Renal dyslipidemia (分担),「そうだったんだ!脂質異常症」2020

    • Author(s)
      中司敦子, 和田淳
    • Total Pages
      262
    • Publisher
      文光堂
    • ISBN
      9784830619489
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-12-25  

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