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Mechanisms of AA amyloid polymerization and tissue deposition

Research Project

Project/Area Number 17K09973
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionNiigata University

Principal Investigator

Kuroda Takeshi  新潟大学, 保健管理・環境安全本部, 教授 (00372475)

Co-Investigator(Kenkyū-buntansha) 上家 潤一  麻布大学, 獣医学部, 教授 (10400269)
中枝 武司  新潟大学, 医歯学系, 講師 (20464000)
和田 庸子  新潟大学, 医歯学総合研究科, 客員研究員 (30608534)
山田 俊幸  自治医科大学, 医学部, 教授 (50211636)
Project Period (FY) 2017-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsアミロイドーシス / 関節リウマチ / 多発性骨髄腫 / 腎機能 / 血清アミロイドA / アイソタイプ / AAアミロイドーシス / アイソフォーム / ALアミロイドーシス / SAAアイソタイプ
Outline of Final Research Achievements

We examined the pattern of amyloid deposition in the renal tissues of AA and AL amyloidosis and clinical data, and found that the deposition pattern of both amyloidoses characterizes renal damage. We also examined SAA isotypes in AA amyloidosis complications. The results showed a high frequency of different isotypes other than the encoded gene. Imaging mass in some cases confirmed the heterogeneous distribution of the various SAA isotypes in the renal specimens. The difference in the deposition pattern between the two amyloidoses was attributed to the weaker polymerization of the precursor protein SAA in AA due to the above-mentioned SAA variations, resulting in the difference in morphology.

Academic Significance and Societal Importance of the Research Achievements

アミロイドーシスはAL,AA、ATTRなど前駆タンパクにより分類されるが重合しアミロイド繊維を形成し組織に沈着することにより臓器障害を引き起こす。AAとALアミロイドーシスは患者数も多く高度な腎障害に進展し透析療法が必要となる場合が多い。一方で臨床病態は異なり形態学的な所見も相違が認められる。ALアミロイドーシスは前駆タンパクの性質上均質であるが、AAでは前駆物質であるSAAに多くのアイソタイプが存在していることが明らかになり腎ではそれらのアイソタイプが各々不均一に存在していることが明らかになった。以上より形態と前駆物質の関係が認められ治療を踏まえて重合を解除する上での一助となる可能性がある。

Report

(7 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2023 2022 2021 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 4 results) Book (2 results)

  • [Journal Article] Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis2022

    • Author(s)
      Naoki Kondo, Takeshi Kuroda, Daisuke Kobayashi
    • Journal Title

      Int. J. Mol. Sci

      Volume: 22 Issue: 20 Pages: 1-27

    • DOI

      10.3390/ijms222010922

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amyloid-specific extraction using organic solvents2020

    • Author(s)
      Kamiie Junichi、Aihara Naoyuki、Uchida Yu、Kobayashi Daiki、Yoshida Yutaka、Kuroda Takeshi、Sakaue Motoharu、Sugihara Yutaka、Rezeli Melinda、Marko-Varga Gy?rgy
    • Journal Title

      MethodsX

      Volume: 7 Pages: 100770-100770

    • DOI

      10.1016/j.mex.2019.100770

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Significant association between renal function and area of amyloid deposition in kidney biopsy specimens from patients with AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis2019

    • Author(s)
      Kuroda Takeshi、Ito Yumi、Imai Naofumi、Nozawa Yukiko、Sato Hiroe、Nakatsue Takeshi、Wada Yoko、Ueno Mitsuhiro、Nakano Masaaki、Narita Ichiei
    • Journal Title

      Amyloid

      Volume: 26 Issue: sup1 Pages: 125-126

    • DOI

      10.1080/13506129.2019.1582512

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Significant association between renal function and area of amyloid deposition in kidney biopsy specimens from patients with AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis2019

    • Author(s)
      Takeshi Kuroda, Yumi Ito, Naofumi Imai, Yukiko Nozawa, Hiroe Sato, Takeshi Nakatsue, Yoko Wada, Mitsuhiro Ueno, Masaaki Nakano, Ichiei Narita.
    • Journal Title

      Amyloid

      Volume: 印刷中

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis2017

    • Author(s)
      Kuroda Takeshi、Tanabe Naohito、Hasegawa Eriko、Wakamatsu Ayako、Nozawa Yukiko、Sato Hiroe、Nakatsue Takeshi、Wada Yoko、Ito Yumi、Imai Naofumi、Ueno Mitsuhiro、Nakano Masaaki、Narita Ichiei
    • Journal Title

      Amyloid

      Volume: 24 Issue: 2 Pages: 123-130

    • DOI

      10.1080/13506129.2017.1338565

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Significant association between renal function and area of amyloid deposition evident in kidney biopsy specimens in both AA and AL amyloidosis.2017

    • Author(s)
      Takeshi Kuroda, Yumi Ito, Naofumi Imai, Yukiko Nozawa, Hiroe Sato, Takeshi Nakatsue, Yoko Wada, Mitsuhiro Ueno, Masaaki Nakano, Ichiei Narita.
    • Journal Title

      Amyloid

      Volume: 24 Issue: sup1 Pages: 151-152

    • DOI

      10.1080/13506129.2017.1291421

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 腎組織に組織学的および生化学的に特異なSAA蛋白のサブタイプを認めた関節リウマチ合併AAアミロイドーシスの1例2023

    • Author(s)
      黒田毅、黒澤陽一他
    • Organizer
      第67回日本リウマチ学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 腎組織に組織学的および生化学的に特異なSAA蛋白のサブタイプを認めた関節リウマチ合併AAアミロイドーシスの1例2021

    • Author(s)
      黒田毅、上家潤一、伊藤由美、今井直史、長谷川絵理子、佐藤弘恵、小林大介、中枝武司、和田庸子、中野正明、成田一衛、山田俊幸
    • Organizer
      第8回日本アミロイドーシス学会学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] Massive renal AA-amyloidosis: a histologically and biochemically distinctive subtype of SAA protein in reactive systemic amyloidosis2020

    • Author(s)
      Takeshi Kuroda, Junichi Kamiie, Yumi Ito, Naofumi Imai, Eriko Hasegawa, Daisuke Kobayashi, Hiroe Sato, Takeshi Nakatsue, Yoko Wada, Masaaki Nakano, Ichiei Narita, Toshiyuki Yamada
    • Organizer
      The XVIIth International Symposiumon Amyloidosis
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Massive renal AA-amyloidosis: a histologically and biochemically distinctive subtype of SAA protein in reactive systemic amyloidosis2020

    • Author(s)
      Takeshi Kuroda, Junichi Kamiie, Yumi Ito, Naofumi Imai, Eriko Hasegawa, Daisuke Kobayashi, Hiroe Sato, Takeshi Nakatsue, Yoko Wada, Masaaki Nakano, Ichiei Narita, Toshiyuki Yamada
    • Organizer
      The XVIth International Symposium on Amyloidosis
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] AAアミロイドーシスの腎障害と臨床病理学的検討2019

    • Author(s)
      黒田 毅
    • Organizer
      第7回アミロイドーシス学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Significant association between renal function and area of amyloid deposition in kidney biopsy specimens from patients with AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis2018

    • Author(s)
      Takeshi Kuroda, Yumi Ito, Naofumi Imai, Yukiko Nozawa, Hiroe Sato, Takeshi Nakatsue, Yoko Wada, Mitsuhiro Ueno, Masaaki Nakano, Ichiei Narita.
    • Organizer
      The XVIth International Symposium on Amyloidosis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Significant association between renal function and area of amyloid deposition in kidney biopsy specimena in both AA and AL amyloidosis2017

    • Author(s)
      Kuroda Takeshi、Ito Yumi、Imai Naofumi、Nozawa Yukiko、Sato Hiroe、Nakatsue Takeshi、Wada Yoko、Ueno Mitsuhiro、Nakano Masaaki、Narita Ichiei
    • Organizer
      The XVIth International Symposium on Amyloidosis
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 関節リウマチに合併するAAアミロイドーシスとALアミロイドーシスの腎組織所見の検討2017

    • Author(s)
      黒田毅、野澤由貴子、佐藤弘恵、中枝武司、和田庸子、伊藤由美、今井直史、中野正明、成田一衛
    • Organizer
      第5回日本アミロイドーシス研究会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 関節リウマチ合併AAアミロイドーシスとALアミロイドーシスの腎生検組織におけるアミロイド沈着量、臨床所見、腎組織学的所見の検討2017

    • Author(s)
      黒田毅、野澤由貴子、佐藤弘恵、中枝武司、和田庸子、伊藤由美、今井直史、中野正明、成田一衛
    • Organizer
      第61回日本リウマチ学会総会
    • Related Report
      2017 Research-status Report
  • [Book] AAアミロイドーシス診療ファイル2022

    • Author(s)
      山田俊幸、右田清志、奥田泰章、黒田毅、中村正
    • Total Pages
      138
    • Publisher
      金芳堂
    • ISBN
      9784765319164
    • Related Report
      2022 Annual Research Report
  • [Book] Lupus2017

    • Author(s)
      Takeshi Kuroda, Hiroe Sato
    • Total Pages
      18
    • Publisher
      InTech
    • ISBN
      9789535131809
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2024-01-30  

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