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Liquid microanatomy to discover the renal injury markers from exosome-derived microRNAs in primitive urine

Research Project

Project/Area Number 18H02331
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionHokkaido University

Principal Investigator

Ichii Osamu  北海道大学, 獣医学研究院, 准教授 (60547769)

Co-Investigator(Kenkyū-buntansha) 昆 泰寛  北海道大学, 獣医学研究院, 教授 (10178402)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords慢性腎臓病 / 獣医学 / イヌ / ネコ / エクソソーム / Liquid Biopsy / miRNA / 尿 / 腎臓 / 伴侶動物 / バイオマーカー / 疾患モデル動物 / 原尿 / レーザーマイクロダイセクション / 汎動物学 / RNA / 腎
Outline of Final Research Achievements

The number of kidney disease cases is increasing in both animals and humans. The technology for non-invasive diagnosis and evaluation of therapeutic effects using biomarkers in body fluids is called Liquid Biopsy, and its clinical application is expected. In this study, we focused on exosomes as a molecule that can realize Liquid Biopsy in the kidney. The results of this study suggested the presence of exosomes in the dilated tubular lumen (including the primary urine) in the early stage of renal injury. The exosomes appeared in urine and contained microRNAs. In particular, elevated urinary miR-21 was considered to indicate tubulointerstitial lesions. On the other hand, elevated blood miR-21 was also associated with glomerular podocyte injury, suggesting that the pathological significance of blood and urine miR-21 is different.

Academic Significance and Societal Importance of the Research Achievements

ヒトの慢性腎臓病は8人に1人が罹患する国民病であり、本国の血液透析導入率は世界一である。獣医療も同様の問題を抱え、特に15歳以上のネコでは30%以上の個体が慢性腎臓病を患う。ヒト、動物ともに血中クレアチニンや尿素窒素等は腎機能の評価には有用だが、Liquid Biopsy(非侵襲的に診断や治療効果の判定等を行う技術)の実現には、高い臓器特異性・早期検出を実現する複数マーカーの探索が必要である。これらの問題解決のため、本研究では腎臓内の微量な体液(原尿)に含まれる小さなカプセル(エクソソーム)をマーカー候補とし、その精査を実施した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (28 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (2 results) Remarks (2 results)

  • [Int'l Joint Research] Sher-e-Bangla Agricultural University(バングラデシュ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Zagazig University(エジプト)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Podocyte Injury Through Interaction Between Tlr8 and Its Endogenous Ligand miR-21 in Obstructed and Its Collateral Kidney2021

    • Author(s)
      Masum Md. Abdul, Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon
    • Journal Title

      Frontiers in Immunology

      Volume: 11 Pages: 606488-606488

    • DOI

      10.3389/fimmu.2020.606488

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Altered clinicopathology and renal pathology in dogs treated with a clinical dose of cisplatin2021

    • Author(s)
      Mari Okamoto, Osamu Ichii, Keiichiro Mie, Hidetaka Nishida, Hideo Akiyoshi
    • Journal Title

      Japanese Journal of Veterinary Research

      Volume: 69 Pages: 109-124

    • NAID

      120007044479

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype2021

    • Author(s)
      Yuki Otani, Osamu Ichii, Masum Md. Abdul, Takashi Namba, Teppei Nakamura, Yasuhiro Kon
    • Journal Title

      Experimental Biology and Medicine

      Volume: なし Issue: 11 Pages: 153537022199601-153537022199601

    • DOI

      10.1177/1535370221996010

    • NAID

      120007126038

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Age-related glomerular lesions with albuminuria in male cotton rats.2020

    • Author(s)
      Ichii O, Nakamura T, Irie T, Otani Y, Hosotani M, Masum MA, Islam RM, Horino T, Sunden Y, Elewa YHA, Kon Y.
    • Journal Title

      Histochem Cell Biol

      Volume: 153 Issue: 1 Pages: 27-36

    • DOI

      10.1007/s00418-019-01824-1

    • NAID

      120006950872

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immune-associated renal disease found in caspase 3-deficient mice.2020

    • Author(s)
      Suzuki T, Ichii O, Nakamura T, Horino T, Elewa YHA, Kon Y.
    • Journal Title

      Cell Tissue Res.

      Volume: 379 Issue: 2 Pages: 323-335

    • DOI

      10.1007/s00441-019-03084-w

    • NAID

      120006955191

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Abnormal Morphology of Distal Tubular Epithelial Cells Is Regulated by Genetic Factors Derived from Mouse Chromosome 122018

    • Author(s)
      Ichii Osamu、Nakamura Teppei、Horino Taro、Yabuki Akira、Elewa Yaser H.A.、Kon Yasuhiro
    • Journal Title

      The American Journal of Pathology

      Volume: 188 Issue: 9 Pages: 2120-2138

    • DOI

      10.1016/j.ajpath.2018.05.011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Urinary Exosome-Derived microRNAs Reflecting the Changes in Renal Function in Cats2018

    • Author(s)
      Ichii Osamu、Ohta Hiroshi、Horino Taro、Nakamura Teppei、Hosotani Marina、Mizoguchi Tatsuya、Morishita Keitaro、Nakamura Kensuke、Sasaki Noboru、Takiguchi Mitsuyoshi、Sato Ryo、Oyamada Kazuhisa、Yaser Hosny Ali Elewa、Kon Yasuhiro
    • Journal Title

      Frontiers in Veterinary Science

      Volume: 5 Pages: 289-289

    • DOI

      10.3389/fvets.2018.00289

    • NAID

      120006551595

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 加齢のInterleukin 36受容体欠損マウスで観察される上皮組織の形態異常2021

    • Author(s)
      難波貴志、市居 修、中村鉄平、大谷祐紀、Masum Md. Abdul、Yaser Hosny Ali Elewa、昆泰寛
    • Organizer
      第1回日本獣医解剖アカデミア
    • Related Report
      2020 Annual Research Report
  • [Presentation] 自己免疫疾患モデルマウスの解析からみる腎臓内IL-36群の機能的棲み分け2020

    • Author(s)
      難波貴志、市居修、中村鉄平、大谷祐紀 、Md. Abdul Masum、Yaser Hosny Ali Elewa、昆泰寛
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] アンドロゲンは自己免疫性腎炎モデルマウスの糸球体硬化を増悪させる2020

    • Author(s)
      大谷祐紀、市居修、Md. Abdul Masum、難波貴志、昆泰寛
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 平松栞、市居修、難波貴志、大谷祐紀、Md. Abdul Masum、中村鉄平、Yaser Hosny Ali Elewa、昆泰寛2020

    • Author(s)
      自己免疫疾患モデルマウスを用いた糖尿病性腎臓病の病態解明アプローチ
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Podocyte injury via Toll-like receptor 8 signaling in experimental obstructive nephropathy in mice2020

    • Author(s)
      Md. Abdul Masum、市居修、Yaser Hosny Ali Elewa、昆泰寛
    • Organizer
      第163回日本獣医学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Enhanced IL-36α expression in the kidneys of autoimmune disease-prone mice2020

    • Author(s)
      Takashi Namba
    • Organizer
      The 9th Sapporo Summer Symposium for One Health
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Orchidectomized autoimmune disease model mouse shows ameliorated sclerotic lesion in the glomerulus2020

    • Author(s)
      Yuki Otani
    • Organizer
      The 9th Sapporo Summer Symposium for One Health
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 走査型顕微鏡の応用的手法による腎病理評価2019

    • Author(s)
      市居 修
    • Organizer
      日本顕微鏡学会第62回シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Application of virtual slide system to histological education in Hokkaido University2019

    • Author(s)
      Osamu Ichii, Yaser Hosny Ali Elewa, Yasuhiro Kon
    • Organizer
      The 7th Congress of Asian Association of Veterinary Anatomists
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自己免疫疾患モデルマウスで変化する腎臓内 Interleukin 1 family の発現バランス2019

    • Author(s)
      難波 貴志, 市居 修, 中村 鉄平, Yaser Hosny Ali Elewa, 昆 泰寛
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 犬におけるシスプラチン投与による腎傷害と臨床病理学的パラメータの変動2019

    • Author(s)
      岡本茉里, 市居 修, 三重慧一郎, 西田英高, 秋吉秀保
    • Organizer
      第12回日本獣医腎泌尿器学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 蛋白尿―糸球体の形態機能とその制御分子から―2019

    • Author(s)
      市居修
    • Organizer
      第15回日本獣医内科学アカデミー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ネコの尿中exosomeに含まれるマイクロRNAの解析2018

    • Author(s)
      市居修、大田寛、堀野太郎、中村鉄平、細谷実里奈、溝口達也、森下啓太郎、中村健介、佐々木東、滝口満喜、佐藤遼、小山田和央、昆泰寛
    • Organizer
      第11回日本獣医腎泌尿器学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新たな腎病態マーカー分子の発見と臨床獣医学への応用に関する研究2018

    • Author(s)
      市居修
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 動物の尿路に出現するリンパ組織(Urinary tract-associated lymphoid tissue, UTALT)2018

    • Author(s)
      市居修、中村鉄平、細谷実里奈、堀野太郎、Yaser Hosny Ali Elewa、昆泰寛
    • Organizer
      第161回日本獣医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Book] 獣医組織学第8版2020

    • Author(s)
      日本獣医学会編(昆泰寛、市居修他)
    • Total Pages
      416
    • Publisher
      学窓社
    • ISBN
      9784873627731
    • Related Report
      2019 Annual Research Report
  • [Book] 獣医解剖・組織・発生学2019

    • Author(s)
      日本獣医解剖学会編(全体:小川和重ら編、解剖・腎臓:市居修)
    • Total Pages
      553
    • Publisher
      学窓社
    • ISBN
      9784873627656
    • Related Report
      2018 Annual Research Report
  • [Remarks] 北海道大学大学院獣医学研究院・獣医学部解剖学教室ホームページ

    • URL

      https://www.vetmed.hokudai.ac.jp/organization/anat/

    • Related Report
      2020 Annual Research Report
  • [Remarks] 北大・獣医・解剖学教室ホームページ

    • URL

      https://www.vetmed.hokudai.ac.jp/organization/anat/

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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