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Ameriolation of progression of polycystic kidney disease by stabilization of renal vessel disorders and exploration of endogenous retrovirus responses in macrophages

Research Project

Project/Area Number 16K11058
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionNara Medical University

Principal Investigator

Ishibashi Michio  奈良県立医科大学, 医学部, 研究員 (40107032)

Co-Investigator(Kenkyū-buntansha) 東原 英二  杏林大学, 医学部, 特任教授 (00092312)
長尾 静子  藤田医科大学, 疾患モデル教育研究施設, 教授 (20183527)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Keywordspolycystic kidney / pericyte / 内在性レトロウイルス / Gag遺伝子 / HIF / 多発性嚢胞腎 / PCKラット / ペリサイト / NG2 / HIF-1 / ベンゾイソフラノン誘導体 / CD31 / PCKラット / ベンゾイソフラノン化合物 / 血管保護 / マクロファージ
Outline of Final Research Achievements

Using PCK rat model and the novel isobenzofuranone compound, NK0070, for 15 weeks administration, the morphological findings of PCK kidneys demonstrated the amelioration of narrowing and dilatation of descending vasa recta (DVR) between the outer medulla and the base of papilla, in which narrowing and dilatation of DVR were minimized and NG2 of pericyte marker was stained keeping around DVR. Furthermore, the lesions of glomerular capillary lumen of juxtamedullary glomeruli such as dilatation and hyalinosis was also ameliorated. Mlana of Gag genes of endogenous retrovirus, in addition to TET enzyme and HIF-1, of NK0070-treated PCK rat kidneys were studies.

Academic Significance and Societal Importance of the Research Achievements

新規イソベンゾフラノン低分子化合物、NK0070により血管新生、血管保護にかかわるpericytes とGalectin-3、転写因子HIF-1にくわえLTR(Long-terminal Repeat)をもつ内在性レトロウイルスGag遺伝子:RTL1, Mlanaの関与を検討した。臓器障害への有用な修復に向かわせる宿主の応答機構としてLTRを有す内在性レトロウイルスの存在と臨床上の意義付けを与え、新規化合物創薬などふくめ新しい修復再生治療の手がかりとなる可能性がある。

Report

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

    (2 results)

All 2019 2018

All Presentation (2 results)

  • [Presentation] NG2活性化による腎髄質ペリサイト機能温存とラットPCK 多発性嚢胞腎モデルにみられる糸球体病変の軽減2019

    • Author(s)
      熊本海生航、釘田雅則、吉村文、藤本清秀、千原良友、小島直人、東原英二、長尾静子、石橋道男
    • Organizer
      第62回日本腎臓学会学術総会、2019年6月21日 名古屋
    • Related Report
      2018 Annual Research Report
  • [Presentation] 多発性嚢胞腎ラットへの低分子化合物NK0070投与によるNG2 pericyte マーカーの温存と腎病変2018

    • Author(s)
      石橋道男、釘田雅則、熊本海生航、吉村 文、 藤本清秀、東原英二、長尾静子
    • Organizer
      第48回日本腎臓学会東部学術大会、平成30年(2018)10月20日~21日、東京
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-07-01  

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