• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Transcriptional regulatory systems controlling renal tubular endocytosis

Research Project

Project/Area Number 21K07861
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionThe University of Tokyo

Principal Investigator

Harita Yutaka  東京大学, 医学部附属病院, 准教授 (10451866)

Co-Investigator(Kenkyū-buntansha) 神田 祥一郎  東京大学, 医学部附属病院, 講師 (60632651)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords腎尿細管 / エンドサイトーシス / Fanconi症候群 / 尿細管 / HNF4a / 尿細管機能異常症 / HNF4A
Outline of Research at the Start

HNF4A遺伝子変異は若年発症成人型糖尿病1 (MODY1)を引き起こす。一方でHNF4AのR76W変異では転写活性が低下するHNF4Aの他の変異と異なり小児期よりFanconi症候群を呈する。本研究ではHNF4A R76W変異により制御される特異的な下流シグナルを明らかにすることを目的に、腎尿細管におけるエンドサイトーシス機序の詳細を細胞モデルおよびマウスモデルを用いて解析する。本研究の成果は転写調節による尿細管の機能制御メカニズムを明らかにするものであり、尿細管機能異常症の分子病態の解明につながる。

Outline of Final Research Achievements

Disrupted reabsorption in the renal proximal tubules leads to Fanconi syndrome. Mutations in HNF4A, which encodes the transcription factor HNF4α, cause juvenile-onset adult-onset diabetes mellitus. Noticeably, HNF4A R76W mutation, unlike other HNF4A mutations, causes Fanconi syndrome. This study aims to clarify its downstream and to elucidate the molecular network involved in tubular reabsorption.
Using a cultured cell model, we identified molecules whose transcription is promoted by HNF4A and further altered by R76W mutation. Of those identified, we focused on candidate factor X, whose function is unknown. We generated knockout mice for X and found that heterozygous knockout mice had no phenotype. The homozygous knockout mice exhibited Fanconi syndrome, indicating that X has an essential function in the kidney. RNA-seq and renal tissue staining of renal tissue revealed variable expression of several molecules associated with endocytosis in the tubules.

Academic Significance and Societal Importance of the Research Achievements

腎臓は血液をろ過して老廃物を除去する重要な器官です。尿細管とよばれる管では一度尿にろ過された物質を再吸収・再利用するプロセスが行われており、エンドサイトーシスと呼ばれます。体内の物質バランスを維持する上で不可欠な機能のため、その異常は、さまざまな腎疾患の発症に関与することが知られています。
本研究は遺伝子異常で起こる腎尿細管エンドサイトーシスの異常に着目し、そのメカニズムを明らかにすることを目的にしています。
腎尿細管の再吸収機構の理解は、腎臓病の予防や治療法の開発に重要な知見の基盤となると考えられます。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (15 results)

All 2024 2023 2022 2021

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Post-renal Biopsy Retroperitoneal Haematoma Accompanied by Decreased Coagulation Factor XIII Levels in Immunoglobulin A Nephropathy2024

    • Author(s)
      Hirano Y, Kanda S, Hidaka M, Kato M, Nishikawa M, Yatomi Y, Tanaka H, Kinumaki A, Kajiho Y, Harita Y
    • Journal Title

      Cureus

      Volume: 16

    • DOI

      10.7759/cureus.54026

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Urinary extracellular vesicles in childhood kidney diseases2023

    • Author(s)
      Harita Yutaka
    • Journal Title

      Pediatric Nephrology

      Volume: - Issue: 8 Pages: 2293-2300

    • DOI

      10.1007/s00467-023-06243-y

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Enzyme-linked immunosorbent assay to detect surface marker proteins of extracellular vesicles purified from human urine2023

    • Author(s)
      Takizawa Keiichi、Nishimura Tatsuya、Harita Yutaka
    • Journal Title

      STAR Protocols

      Volume: 4 Issue: 3 Pages: 102415-102415

    • DOI

      10.1016/j.xpro.2023.102415

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Infective endocarditis‐associated glomerulonephritis due to Streptococcus gallolyticus subsp. pasteurianus2023

    • Author(s)
      Takahashi Kenichiro、Kajiho Yuko、Kinumaki Akiko、Ogawa Yosuke、Kanda Shoichiro、Inuzuka Ryo、Harita Yutaka
    • Journal Title

      Pediatrics International

      Volume: 65 Issue: 1

    • DOI

      10.1111/ped.15584

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Comparison of bleeding complications after pediatric kidney biopsy between intravenous sedation and general anesthesia: a nationwide cohort study2023

    • Author(s)
      Okada Akira、Ikeda Kurakawa Kayo、Harita Yutaka、Shimizu Akira、Yamaguchi Satoko、Aso Shotaro、Ono Sachiko、Hashimoto Yohei、Kumazawa Ryosuke、Michihata Nobuaki、Jo Taisuke、Matsui Hiroki、Fushimi Kiyohide、Nangaku Masaomi、Yamauchi Toshimasa、Yasunaga Hideo、Kadowaki Takashi
    • Journal Title

      BMC Pediatrics

      Volume: 23 Issue: 1 Pages: 33-33

    • DOI

      10.1186/s12887-022-03828-8

    • Related Report
      2022 Research-status Report
  • [Journal Article] Urinary extracellular vesicles signature for diagnosis of kidney disease2022

    • Author(s)
      Takizawa Keiichi、Ueda Koji、Sekiguchi Masahiro、Nakano Eiji、Nishimura Tatsuya、Kajiho Yuko、Kanda Shoichiro、Miura Kenichiro、Hattori Motoshi、Hashimoto Junya、Hamasaki Yuko、Hisano Masataka、Omori Tae、Okamoto Takayuki、Kitayama Hirotsugu、Fujita Naoya、Kuramochi Hiromi、Ichiki Takanori、Oka Akira、Harita Yutaka
    • Journal Title

      iScience

      Volume: 25 Issue: 11 Pages: 105416-105416

    • DOI

      10.1016/j.isci.2022.105416

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of right hypodysplastic kidney and ectopic ureter associated with bicornuate uterus in a prepubertal girl2022

    • Author(s)
      Nakamura Misako、Kanda Shoichiro、Kajiho Yuko、Hinata Munetoshi、Tomonaga Kotaro、Fujishiro Jun、Harita Yutaka
    • Journal Title

      CEN Case Reports

      Volume: 12 Issue: 1 Pages: 122-129

    • DOI

      10.1007/s13730-022-00730-1

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Precise clinicopathologic findings for application of genetic testing in pediatric kidney transplant recipients with focal segmental glomerulosclerosis/steroid-resistant nephrotic syndrome2022

    • Author(s)
      Miura Kenichiro、Kaneko Naoto、Hashimoto Taeko、Ishizuka Kiyonobu、Shirai Yoko、Hisano Masataka、Chikamoto Hiroko、Akioka Yuko、Kanda Shoichiro、Harita Yutaka、Yamamoto Toshiyuki、Hattori Motoshi
    • Journal Title

      Pediatric Nephrology

      Volume: 38 Issue: 2 Pages: 417-429

    • DOI

      10.1007/s00467-022-05604-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel de novo truncating TRIM8 variant associated with childhood-onset focal segmental glomerulosclerosis without epileptic encephalopathy: a case report2021

    • Author(s)
      Shirai Yoko、Miura Kenichiro、Kaneko Naoto、Ishizuka Kiyonobu、Endo Amane、Hashimoto Taeko、Kanda Shoichiro、Harita Yutaka、Hattori Motoshi
    • Journal Title

      BMC Nephrology

      Volume: 22 Issue: 1 Pages: 417-417

    • DOI

      10.1186/s12882-021-02626-1

    • NAID

      120007181370

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An infant with X-linked anhidrotic ectodermal dysplasia with immunodeficiency presenting with Pneumocystis pneumonia: A case report.2021

    • Author(s)
      Toyohara M, Kajiho Y, Toyofuku E, Takahashi C, Owada K, Kanda S, Harita Y, Ohnishi H, Wada T, Imai K, Kanegane H, Morio T, Oka A
    • Journal Title

      Clin Case Rep

      Volume: 9 Issue: 11

    • DOI

      10.1002/ccr3.5093

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Degree of foot process effacement in patients with genetic focal segmental glomerulosclerosis: a single-center analysis and review of the literature2021

    • Author(s)
      Ishizuka K, Miura K, Hashimoto T, Kaneko N, Harita Y, Yabuuchi T, Hisano M, Fujinaga S, Omori T, Yamaguchi Y, Hattori M.
    • Journal Title

      Sci Rep

      Volume: 11 Issue: 1 Pages: 12008-12008

    • DOI

      10.1038/s41598-021-91520-9

    • NAID

      120007183298

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A case of 17q12 deletion syndrome that presented antenatally with markedly enlarged kidneys and clinically mimicked autosomal recessive polycystic kidney disease2021

    • Author(s)
      Nakamura Misako、Kanda Shoichiro、Kajiho Yuko、Morisada Naoya、Iijima Kazumoto、Harita Yutaka
    • Journal Title

      CEN Case Reports

      Volume: 10 Issue: 4 Pages: 543-548

    • DOI

      10.1007/s13730-021-00604-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Establishment of a novel mouse model of renal Fanconi syndrome2023

    • Author(s)
      Takeshi Nagasawa, Hiromi Takizawa, Keiichi Takizawa Yuko Kajiho, Shoichiro Kanda, Motohiro Kato, Yutaka Harita
    • Organizer
      The 18th Congress of Asian Society for Pediatric Research
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HNF4αによる変異特異的尿細管機能制御機構の解明2022

    • Author(s)
      長澤 武、滝澤 ひろみ、滝澤 慶一、梶保 祐子、神田 祥一郎、張田 豊
    • Organizer
      第30回発達腎研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] 遺伝性腎疾患研究最前線:国内で行われている最先端の研究に触れる ネフロン全体から見た蛋白尿発症の分子メカニズム2021

    • Author(s)
      張田豊
    • Organizer
      日本腎臓学会学術集会
    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi