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Novel transgenic mice, Erythropoietin-CreERT2 mice, label unique subpopulations of renal fibroblasts

Research Project

Project/Area Number 15K09259
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionKyoto University

Principal Investigator

Endo Shuichiro  京都大学, 医学研究科, 助教 (80533380)

Co-Investigator(Kenkyū-buntansha) 柳田 素子  京都大学, 医学研究科, 教授 (70378769)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords腎線維化 / 腎性貧血 / 線維芽細胞 / エリスロポエチン
Outline of Final Research Achievements

Erythropoietin (Epo) is produced by a small subpopulation of resident fibroblasts in the healthy kidney and renal anemia is on of the complications of chronic kidney disease (CKD). It has not been fully elucidated whether Epo-producing cells are the distinct and specialized subpopulation of resident fibroblasts, or all resident fibroblasts possess the capacity to produce Epo. Here we generated a novel mouse strain, EpoCreERT2/+ mice, which label Epo-producing cells at the desired time points, and examined the behaviors of Epo-producing cells. Utilizing this mouse strain, we showed that Epo-producing cells maintained Epo-producing ability and proliferated during fibrosis, indicating that Epo-producing cells are the distinct population of renal fibroblasts. Further analysis of the Epo-producing cell population will lead to new therapeutic approach to renal anemia.

Academic Significance and Societal Importance of the Research Achievements

新規遺伝子組換えマウスEpo-CreERT2マウスを作製し、任意の時点でEpo産生細胞を標識することに成功した。このマウスを用いて、成体腎におけるEpo産生細胞が線維化腎でmyofibroblastに形質転換することを初めて証明した。さらに特定の細胞が繰り返しEpo産生を担う可能性やEpo産生細胞が他の線維芽細胞と比べて増殖しやすい可能性が示唆され、Epo産生細胞は線維芽細胞における特殊な細胞集団である可能性が示唆された。今後、Epo産生細胞集団の解析を進め、腎性貧血の機序の解明と新規治療法開発に繋げたい。

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (2 results)

All 2018 2017

All Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] Novel transgenic mice, Erythropoietin-CreERT2 mice, label unique subpopulations of renal fibroblasts2018

    • Author(s)
      Keiichi Kaneko, Misako Asada, Shuichiro Endo, Motoko Yanagita
    • Organizer
      ISN Frontiers meetings
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Lineage tracing study defines erythropoietin-producing cells as the distinct subpopulation of resident fibroblasts with unique behaviors2017

    • Author(s)
      Keiichi Kaneko, Misako Asada, Shuichiro Endo, Motoko Yanagita
    • Organizer
      American Society of Nephrology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2022-01-27  

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