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Cell Therapy on Chronic Kidney Diseases by Inducible Podocytes from Somatic Cells

Research Project

Project/Area Number 17K19643
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field General internal medicine and related fields
Research InstitutionChiba University

Principal Investigator

Yokote koutaro  千葉大学, 大学院医学研究院, 教授 (20312944)

Co-Investigator(Kenkyū-buntansha) 前澤 善朗  千葉大学, 大学院医学研究院, 講師 (80436443)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Keywordsポドサイト / 慢性腎臓病 / 細胞治療 / 転写因子 / 分化 / 再生医学 / 糖尿病
Outline of Final Research Achievements

Although we aimed to create podocytes from somatic cells by Direct reprogramming and to make new cell therapy, it was difficult due to problems with the evaluation system. On the other hand, we analyzed renal interstitial fibrosis, which is an important mechanism of chronic kidney disease. The results suggested that Tcf21, a common regulator of podocytes and stroma, is upregulated during interstitial fibrosis, and that supression of this gene may lead to decreased fibrosis. Therefore, Tcf21 is considered promising as a new therapeutic target for chronic kidney disease.

Academic Significance and Societal Importance of the Research Achievements

腎糸球体の蛋白ろ過装置の主体である、ポドサイトを、皮膚や脂肪細胞から作成することを試みたが、いくつかの障壁があり困難であった。一方この検討の過程で、ポドサイトではなく腎臓髄質の線維化において重要な転写因子Tcf21の機能を見出した。この遺伝子の欠損により、腎臓の細胞外マトリクスの産生が低下することが判明した。多くの慢性腎臓病が終末像として組織の線維化を呈することから、これを抑制しうる機構が見出されたことは重要であると考えている。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (29 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (16 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] Northwestern University Chicago(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Northwestern University Chicago,(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] CXCL12-CXCR4 pathway activates brown adipocytes and induces insulin resistance in CXCR4-deficient mice under high-fat diet2019

    • Author(s)
      Kurita Kenichi、Ishikawa Ko、Takeda Kenji、Fujimoto Masanori、Ono Hiraku、Kumagai Jin、Inoue Hiromi、Yokoh Hidetaka、Yokote Koutaro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 6165-6165

    • DOI

      10.1038/s41598-019-42127-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-Term Efficacy and Safety of Pemafibrate, a Novel SelectivePeroxisome Proliferator-Activated Receptor-α Modulator (SPPARMα),in Dyslipidemic Patients with Renal Impairment2019

    • Author(s)
      Yokote K, Yamashita S, Arai H, Araki E, Suganami H, Ishibashi S, Of TheK-Study Group OB
    • Journal Title

      Int J Mol Sci

      Volume: 20(3) Issue: 3 Pages: 706-706

    • DOI

      10.3390/ijms20030706

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development2018

    • Author(s)
      Ide S, Finer G, Maezawa Y, Onay T, Souma T, Scott R, Ide K, Akimoto Y, Li C,Ye M, Zhao X, Baba Y, Minamizuka T, Jin J, Takemoto M, Yokote K, Quaggin SE
    • Journal Title

      J Am Soc Nephrol

      Volume: 29 Issue: 12 Pages: 2795-2808

    • DOI

      10.1681/asn.2017121278

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells.2018

    • Author(s)
      Nagano H, Hashimoto N, Nakayama A, Suzuki S, Miyabayashi Y, Yamato A, Higuchi S, Fujimoto M, Sakuma I, Beppu M, Yokoyama M, Suzuki Y, Sugano S, Ikeda K, Tatsuno I, Manabe I, Yokote K, Inoue S, Tanaka T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 115 Issue: 33 Pages: 8370-8375

    • DOI

      10.1073/pnas.1804243115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial2018

    • Author(s)
      Araki Eiichi、Yamashita Shizuya、Arai Hidenori、Yokote Koutaro、Satoh Jo、Inoguchi Toyoshi、Nakamura Jiro、Maegawa Hiroshi、Yoshioka Narihito、Tanizawa Yukio、Watada Hirotaka、Suganami Hideki、Ishibashi Shun
    • Journal Title

      Diabetes Care

      Volume: 41 Issue: 3 Pages: 538-546

    • DOI

      10.2337/dc17-1589

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum podocalyxin levels correlate with carotid intima media thickness, implicating its role as a novel biomarker for atherosclerosis2018

    • Author(s)
      Shoji Mayumi、Takemoto Minoru、Kobayashi Kazuki、Shoji Toshihiro、Mori Satoka、Sagara Jun-ichi、Kurosawa Hiroyuki、Hirayama Yoshiaki、Sakamoto Kenichi、Ishikawa Takahiro、Koshizaka Masaya、Maezawa Yoshiro、Yokote Koutaro
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 245-245

    • DOI

      10.1038/s41598-017-18647-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Approach to the Treatment of Plasma Protein Deficiency: <i>Ex Vivo</i>-Manipulated Adipocytes for Sustained Secretion of Therapeutic Proteins2018

    • Author(s)
      Kuroda Masayuki、Saito Yasushi、Aso Masayuki、Yokote Koutaro
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 66 Issue: 3 Pages: 217-224

    • DOI

      10.1248/cpb.c17-00786

    • NAID

      130006407125

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of a novel selective peroxisome proliferator-activated receptor α modulator, pemafibrate (K-877), on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance2018

    • Author(s)
      Matsuba Ikuro、Matsuba Ren、Ishibashi Shun、Yamashita Shizuya、Arai Hidenori、Yokote Koutaro、Suganami Hideki、Araki Eiichi
    • Journal Title

      Journal of Diabetes Investigation

      Volume: - Issue: 6 Pages: 0-0

    • DOI

      10.1111/jdi.12845

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sitagliptin but not alpha glucosidase inhibitor reduced the serum soluble CD163, a marker for activated macrophage, in individuals with type 2 diabetes mellitus.2017

    • Author(s)
      Hattori A, Takemoto M, Tokuyama H, Koshizaka M, Yokote K.
    • Journal Title

      Diabetes Res Clin Pract.

      Volume: 126 Pages: 138-143

    • DOI

      10.1016/j.diabres.2017.02.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Femoral osteoporosis is more common than lumbar osteoporosis in patients with Werner syndrome2017

    • Author(s)
      Mori Seijiro、Zhou Heying、Yamaga Masaya、Takemoto Minoru、Yokote Koutaro
    • Journal Title

      Geriatr Gerontol Int.

      Volume: 17 Issue: 5 Pages: 854-856

    • DOI

      10.1111/ggi.12960

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack2017

    • Author(s)
      Yoshida Y、Wang H、Hiwasa T、Machida T、Kobayashi E、Mine S、Tomiyoshi G、Nakamura R、Shinmen N、Kuroda H、Takizawa H、Kashiwado K、Kamitsukasa I、Shin H、Wada T、Aotsuka A、Nishi E、Ohno M、Takemoto M、Yokote K、Takahashi S、Matsushima J、Zhang Xiao-Meng、Takiguchi M、Iwadate Y
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 10 Pages: 8836-8848

    • DOI

      10.18632/oncotarget.23653

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Human model of accelerated aging and atherosclerosis2018

    • Author(s)
      Yokote K
    • Organizer
      18th International symposium on atherosclerosis
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Overview of clinical trials with a SPPARMα in patients with dyslipidaemia: Japanese and European experience2018

    • Author(s)
      Yokote K
    • Organizer
      International Atherosclerosis Society Joint Symposium:The Selective Peroxisome Proliferator-Activated Receptor Alpha Modulator (SPPARMα) Concept
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comparing the Effects of Ipragliflozin and Metformin on Visceral Fat Reduction in Patients with Type 2 Diabetes Inadequately Controlled with Sitagliptin-A Prospective, Multicenter, Blinded-Endpoint, Randomized Controlled Study in Japan (PRIME-V Study)2018

    • Author(s)
      Koshizaka M, Yokote K et al
    • Organizer
      the American Diabetes Association's 78th Scientific Sessions
    • Related Report
      2018 Annual Research Report
  • [Presentation] Comparison of ipragliflozin and metformin for visceral fat reduction in elderly patients with type 2 diabetes: a prospective, blinded-endpoint, randomised controlled study2018

    • Author(s)
      Koshizaka M, Yokote K et al
    • Organizer
      European Association for the Study of Diabetes 54th Annual Meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] 転写因子Tcf21は腎臓発生においてGdnf経路を介して尿管芽の分岐を制御する2018

    • Author(s)
      井出真太郎、前澤善朗、Gal Finer、Rizaldy Scott、Tuncer Ona、竹本稔、秋元義弘、 Susan Quaggin、横手幸太郎
    • Organizer
      第55回日本臨床分子医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 血中ポドカリキシン(Podocalyxin:Podxl)値と頸動脈内膜中膜肥厚度(IMT)との関連についての検討2018

    • Author(s)
      正司真弓、前澤善朗、竹本稔、小林一貴、越坂理也、石川崇広、井出真太郎、井出佳奈、横手幸太郎
    • Organizer
      第116回日本内科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖尿病腎症における転写調節因子Tcf21の機能解析2018

    • Author(s)
      井出真太郎、前澤善朗、Scott Rizardy、Onay Tuncerm、井出佳奈、竹本稔、秋元義弘、Susan Quaggin、横手幸太郎
    • Organizer
      第61回日本糖尿病学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 転写因子Tcf21の糖尿病大血管障害における役割2018

    • Author(s)
      南塚拓也、前澤善朗、馬場雄介、井出真太郎、石川崇広、越坂理也、横手幸太郎
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Tcf21は心負荷時の線維化を制御する―糖尿病性心筋症との関連2018

    • Author(s)
      馬場 雄介、前澤 善朗、南塚 拓也、井出 真太郎、近藤 尚通、小林 欣夫、横手 幸太郎
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Efficacy and Long-term Safety of Omega-3 Free Fatty Acids, Epanova, in Japanese Patients with Dyslipidemia, 口頭2018

    • Author(s)
      横手幸太郎
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 糖尿病腎症の腎線維化における転写因子Tcf21の機能解析2017

    • Author(s)
      井出真太郎、前澤善朗、井出佳奈、竹本稔、横手幸太郎
    • Organizer
      第60回日本糖尿病学会年次術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 血管合併症予防のための脂質トータルマネージメント, 口頭2017

    • Author(s)
      横手幸太郎
    • Organizer
      第60回日本糖尿病学会年次学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 転写因子Tcf21は尿管芽の分岐を制御し、腎臓発生において必須である2017

    • Author(s)
      井出真太郎、前澤善朗、井出佳奈、竹本稔、横手幸太郎
    • Organizer
      第60回日本腎臓学会年次術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 糖尿病・肥満の脂質管理と残存リスク, 口頭,2017

    • Author(s)
      横手幸太郎
    • Organizer
      第49回日本動脈硬化学会総会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 経過中に乾癬を合併し、肥満治療によりTh17 細胞の減少が見られた高度肥満症、2 型糖尿病の一例2017

    • Author(s)
      前澤善朗、遠藤裕介、松岡悠美、横手幸太郎
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 転写調節因子Tcf21 は心臓負荷時の線維化を制御する2017

    • Author(s)
      馬場雄介、前澤善朗、竹本稔、横手幸太郎
    • Organizer
      第32 回日本糖尿病合併症学会
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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