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The analysis of pathogensis and therapy deveolpment of kidney involvement of monoclonal kappa chain-induced crystal-storing histiocytosis

Research Project

Project/Area Number 16K19485
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionKanazawa University

Principal Investigator

Hara Satoshi  金沢大学, 医学系, 助教 (80749820)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsポドサイト / 軽鎖 / 発現ベクター / トランスジェニックマウス / マクロファージ / 内科 / 病理学 / 蛋白質 / 臨床
Outline of Final Research Achievements

We identified the pathogenic kappa light chain causing crystal-storing histiocytosis and succeeded in producing huge amount of the protein. We confirmed that this pathogenic kappa light chain was endocytosed and crystalized in mice macrophages, podocytes, and proximal tubular cells in vitro. However, we did not determine how the light chain has its toxicity for those cells and the mechanism of kappa light chain integration into those cells. We created transgenic mice which secrete the pathogenic kappa light chain. The transgenic mice formed macrophages containing kappa crystals in spleen, but did not show any kidney involvements of crystal-storing histiocytosis due to small amount of pathogenic kappa light chain secretion.

Academic Significance and Societal Importance of the Research Achievements

マクロファージや近位尿細管のみならず、ポドサイトにも結晶を形成しうる変異軽鎖の配列を同定し、その蛋白精製を行うことができた。今後これを用いて、ポドサイトへの取り込み機序の解明を行うことで、軽鎖によるポドサイト障害の機序ひいては慢性腎臓病の機序解明と治療薬開発へつながる可能性がある。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (1 results)

All 2019

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] A Case Report of Crystalline Light Chain Inclusion-Associated Kidney Disease Affecting Podocytes but Without Fanconi Syndrome: A Clonal Analysis of Pathological Monoclonal Light Chain.2019

    • Author(s)
      20.Ito K*, Hara S*, Yamada K, Zoshima T, Mizushima I, Fujii H, Miyazaki R, Kawai Y, Yachie A, Nagata M, Izui S, Yamagichi M, Kawano M.(*equally contribution)
    • Journal Title

      Medicine

      Volume: 98 Issue: 5 Pages: e13915-e13915

    • DOI

      10.1097/md.0000000000013915

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed

URL: 

Published: 2016-04-21   Modified: 2021-02-19  

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