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Breg-IL-10 system as a novel therapeutic target for CKD

Research Project

Project/Area Number 19K08693
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

FUKAMI KEI  久留米大学, 医学部, 教授 (80309781)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsAKI / IL10 / reperfusion / Breg / IL-10 / IRI / 組織修復 / B cell / Diabetic Nephropathy / Re-perfusion injury
Outline of Research at the Start

糖尿病性腎症進展や急性腎障害から末期腎不全に至る症例は増加の一途を辿っている。これら腎機能低下の主座は、最終共通経路としての細胞浸潤、高度な線維化、尿細管間質障害である。近年様々な腎傷害抑制因子が同定されているが、修復過程を制御する研究はなされていない。B細胞性免疫は腎組織修復に深く関与しているものの、これら腎障害進展における修復過程に制御性B細胞(Breg)-IL-10系がいかに関与し腎保護的に働くかは定かではない。これらが解明されれば、Bregの移入療法が糖尿病性腎症や急性腎障害から末期腎不全への進展を阻止するという新たな腎臓病治療ストラテジーになると考えている。

Outline of Final Research Achievements

In this study, we examined whether IL-10-expressed Breg is associated with the pathogenesis of AKI-to CKD in re-perfusion-induced AKI model IL-10GFP mice. We found that in this AKI model, IL-10 expression was time-dependently decreased in the glomeruli and increased in the renal medulla by IR. Decrease in IL-10 expression in the glomeruli occurred before the progression to glomerulosclerosis in this AKI model. To identify the existence of Breg in the kidney, we stained with CD19, as a B cell marker, and we found the colocalization of IL-10 and CD19 in the mesangial area of the glomeruli. These expression was also diminished by the IR. These findings suggest that mesangial cells might work as a Breg to inhibit the progression to CKD by IR-induced AKI. Breg in the glomeruli might be an important therapeutic target to prevent the progression of AKI-to-CKD.

Academic Significance and Societal Importance of the Research Achievements

近年、AKIは様々な状況で生じることが明らかとなっている。特に高齢者においては動脈硬化による腎虚血からAKIを引き起こし、その後CKDへ移行する。その過程において、尿細管障害が腎障碍の首座と考えられてきたが、我々は糸球体の変化に着目し研究を行った。現状ではAKI-to-CKDへの移行を阻止するための治療法は確立されていない。今回我々は、世界で初めてメサンギウム細胞がBregとして機能していることを見出した。今後はメサンギウム細胞のBregとしての機能解析と治療応用を考えており、新規治療ターゲットとして研究を発展させることは、社会的にも大変意義があることと考える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (21 results)

All 2022 2021 2020 2019

All Journal Article (13 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 13 results,  Open Access: 12 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (4 results)

  • [Journal Article] Effect of tolvaptan on renal involvement in patients with autosomal dominant polycystic kidney disease according to different gene mutations.2021

    • Author(s)
      Moriyama T, Nakayama Y, Soejima M, Yokota Y, Ota K, Ito S, Kodama G, Nakamura N, Kurokawa Y, Yano J, Ueda U, Takamiya Y, Kaida Y, Hazama T, Shibata R, Koda Y, Fukami K.
    • Journal Title

      Clin Exp Nephrol.

      Volume: 25 Issue: 3 Pages: 251-260

    • DOI

      10.1007/s10157-020-01988-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Triple combination therapy with telmisartan, amlodipine, and hydrochlorothiazide ameliorates albuminuria in a normotensive rat remnant kidney model2021

    • Author(s)
      Ito S, Nakayama Y, Kodama G, Ota K, Taguchi K, Yusuke Kaida1, Yamagishi S and Fukami K.
    • Journal Title

      Renal Replacement Therapy 7:16, 2021

      Volume: 7 Pages: 16-16

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and efficacy of single-needle leukocyte apheresis (LCAP) for treatment of ulcerative colitis2020

    • Author(s)
      Shindo Y, Mitsuyama K, Yamasaki H, Imai T, Yoshioka S, Kuwaki K, Yamauchi R, Yoshimura T, Araki T, Morita M, Tsuruta K, Yamasaki S, Fukami K, Torimura T
    • Journal Title

      Therapeutic Apheresis and Dialysis

      Volume: 24 Issue: 5 Pages: 503-510

    • DOI

      10.1111/1744-9987.13539

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] l ‐carnitine supplementation vs cycle ergometer exercise for physical activity and muscle status in hemodialysis patients: A randomized clinical trial2020

    • Author(s)
      Yano Junko、Kaida Yusuke、Maeda Takashi、Hashida Ryuki、Tonan Tatsuyuki、Nagata Shuji、Hazama Takuma、Nakayama Yosuke、Ito Sakuya、Kurokawa Yuka、Otome Takaomi、Shibata Ryo、Tashiro Kyoko、Kakuma Tatsuyuki、Matsuse Hiroo、Fukami Kei
    • Journal Title

      Therapeutic Apheresis and Dialysis

      Volume: - Issue: 3 Pages: 304-313

    • DOI

      10.1111/1744-9987.13576

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new diagnostic indication device of a biomarker growth differentiation factor 15 for mitochondrial diseases: From laboratory to automated inspection2020

    • Author(s)
      Koga Yasutoshi、Povalko Nataliya、Inoue Eisuke、Ishii Akiko、Fujii Katsunori、Fujii Tatsuya、Murayama Kei、Mogami Yukiko、Hata Ikue、Ikawa Masamichi、Fukami Kei、Fukumoto Yoshihiro、Nomura Masatoshi、Ichikawa Kazuki、Yoshida Kaori
    • Journal Title

      Journal of Inherited Metabolic Disease

      Volume: 44 Issue: 2 Pages: 358-366

    • DOI

      10.1002/jimd.12317

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of switching from cinacalcet to etelcalcetide on secondary hyperparathyroidism in patients undergoing hemodialysis: an ESCORT trial.2020

    • Author(s)
      Kurokawa Y, Kaida Y, Hazama T, Nakayama Y, Otome T, Shibata R, Ito S, Kodama G, Nakamura N, Kambe T, Moriyama T, Nagata A, Minami A, Ando R, Wada Y, Sugiyama M, Usui M, Chiba M, Moriyama A, Ohara A, Miyazaki H, Kakuma T, Fukami K.
    • Journal Title

      Renal Replacement Therapy 6:64, 2020

      Volume: 6 Pages: 64-64

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats2020

    • Author(s)
      Nakamura Kazufumi、Akagi Satoshi、Ejiri Kentaro、Yoshida Masashi、Miyoshi Toru、Sakaguchi Masakiyo、Amioka Naofumi、Suastika Luh Oliva Saraswati、Kondo Megumi、Nakayama Rie、Takaya Yoichi、Higashimoto Yuichiro、Fukami Kei、Matsubara Hiromi、Ito Hiroshi
    • Journal Title

      Journal of Cardiology

      Volume: - Issue: 1 Pages: 12-16

    • DOI

      10.1016/j.jjcc.2020.12.009

    • NAID

      120007182876

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Uremic Toxin–Targeting as a Therapeutic Strategy for Preventing Cardiorenal Syndrome2019

    • Author(s)
      Taguchi Kensei、Elias Bertha C.、Brooks Craig R.、Ueda Seiji、Fukami Kei
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 1 Pages: 2-8

    • DOI

      10.1253/circj.CJ-19-0872

    • NAID

      130007772709

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2019-12-25
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kinetics of Serum Carnitine Fractions in Patients with Chronic Kidney Disease Not on Dialysis2019

    • Author(s)
      YANO JUNKO、ITO SAKUYA、KODAMA GOH、NAKAYAMA YOSUKE、KAIDA YUSUKE、YOKOTA YUNOSUKE、KINOSHITA YUKIE、TASHIRO KYOKO、FUKAMI KEI
    • Journal Title

      The Kurume Medical Journal

      Volume: 66 Issue: 3 Pages: 153-160

    • DOI

      10.2739/kurumemedj.MS663001

    • NAID

      130008101716

    • ISSN
      0023-5679, 1881-2090
    • Year and Date
      2019-09-30
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single Needle Granulocyte and Monocyte Apheresis for Ulcerative Colitis: A Retrospective Safety Analysis2019

    • Author(s)
      Imai T, Yamasaki H, Mitsuyama K, Yamaga O, Sugihara G, Kaida Y, Shibata R, Hazama T, Yoshioka S, Torimura T, Fukami K, Yamashita N.
    • Journal Title

      The Kurume Medical Journal

      Volume: 66 Issue: 1 Pages: 1-7

    • DOI

      10.2739/kurumemedj.MS661002

    • NAID

      130007867225

    • ISSN
      0023-5679, 1881-2090
    • Year and Date
      2019-03-31
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集 動脈硬化とカルシウム~カルシウムパラドックスの謎に迫る~ Seminar CKD-MBDにおけるAGEs-RAGE系の役割v2019

    • Author(s)
      Fujisawa H, Nakayama Y, Ueda K, Fukami K
    • Journal Title

      CLINICAL CALCIUM

      Volume: 29 Issue: 2 Pages: 193-198

    • DOI

      10.20837/4201902193

    • ISSN
      0917-5857
    • Year and Date
      2019-02-28
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of cryofiltration and mizoribine combination with oral steroid therapy in a patient with membranoproliferative glomerulonephritis due to essential cryoglobulinemia.2019

    • Author(s)
      Kurokawa Y, Koike K, Kaida Y, Ito S, Chiba H, Urae K, Moriyama T, Nakamura N, Imai T, Shibata R, Hazama T, Wakasugi D, Okuda S, Fukami K
    • Journal Title

      CEN Case Rep

      Volume: 8 Issue: 3 Pages: 205-211

    • DOI

      10.1007/s13730-019-00394-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness of immunosuppressive therapy for nephrotic syndrome in a patient with late-onset Fabry disease: a case report and literature review.2019

    • Author(s)
      Fujisawa H, Nakayama Y, Nakao S, Yamamoto R, Kurokawa Y, Nakamura N, Nagata A, Tsukimura T, Togawa T, Sakuraba H, Fukami K.
    • Journal Title

      BMC Nephrol

      Volume: 20 Issue: 1 Pages: 469-469

    • DOI

      10.1186/s12882-019-1657-7

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Production of the regulatory cytokine IL-10 in renal ischemia-reperfusion injury2022

    • Author(s)
      Yunosuke Yokota, Goh Kodama, Sakuya Ito, Makoto Nasu, Yusuke Kaida, Mitsushi Mizoguchi, Kei Fukami
    • Organizer
      World Congress of Nephrology 2022
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腎虚血再灌流傷害モデルにおける調節性サイトカインIL-10誘導2021

    • Author(s)
      横田祐之介, 児玉豪, 伊藤佐久耶, 那須誠, 甲斐田裕介, 溝口充志, 深水圭
    • Organizer
      日本腎臓学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 糖尿病性腎臓病における心筋障害発症メカニズムと治療を考える2020

    • Author(s)
      深水 圭
    • Organizer
      第63回日本腎臓学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 腹膜透析患者に対する集学的管理2020

    • Author(s)
      深水 圭
    • Organizer
      第65回日本透析医学会学術集会・総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Book] 臨床透析2020

    • Author(s)
      深水 圭
    • Total Pages
      6
    • Publisher
      臨床医学出版
    • Related Report
      2020 Research-status Report
  • [Book] 九州人工透析研究会誌2020

    • Author(s)
      坂口由美子、水落記子、角 昌久、川崎真由美、深水 圭
    • Total Pages
      6
    • Publisher
      -
    • Related Report
      2020 Research-status Report
  • [Book] 九州人工透析研究会誌2020

    • Author(s)
      深水 圭
    • Total Pages
      4
    • Publisher
      -
    • Related Report
      2020 Research-status Report
  • [Book] Pharma Medica2020

    • Author(s)
      田口顕正、深水 圭
    • Total Pages
      6
    • Publisher
      メディカルレビュー社
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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