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The role of hypoxia inducible factor on renal transplantation-induced fibrosis and the establishment of its therapeutic strategies

Research Project

Project/Area Number 21K09433
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionOsaka Metropolitan University (2022-2023)
Osaka City University (2021)

Principal Investigator

Uchida Junji  大阪公立大学, 大学院医学研究科, 教授 (40343412)

Co-Investigator(Kenkyū-buntansha) 鞍作 克之  大阪公立大学, 大学院医学研究科, 講師 (70364007)
大年 太陽  大阪公立大学, 大学院医学研究科, 講師 (40749214)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2023: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腎線維化 / 腎移植 / シングルセル解析 / HIF-PH阻害薬 / HIF-PH阻害剤 / 慢性腎臓病 / HIF-PHD阻害剤
Outline of Research at the Start

腎移植成績において短期的な移植腎生着率は飛躍的に改善した。しかしながら、現在も長期的な移植腎予後は改善したとは言えず、克服すべき課題として移植腎長期生着が挙げられる。様々な因子が移植腎にダメージを与えるが移植腎機能不全に至る過程で共通して認められる病態が腎線維化である。腎障害が進行する過程で腎組織が低酸素に陥り低酸素誘導性因子 Hypoxia inducible factor;HIFが活性化され様々な遺伝子発現を誘導することが知られている。本研究ではHIFを持続活性化させることが知られているプロリン水素化酵素阻害剤;PHD阻害薬を利用して腎線維化に対する治療法開発を目指す。

Outline of Final Research Achievements

It is essential for prolonged-survive of transplanted kidneys to suppress their fibrosis. In this study, we tried to identify the renal fibrosis suppression molecules induced by HIF-PH inhibitors. We have extracted the fibrosis related molecules expressed from the early stage through the single cell analyses of the fibrotic kidneys induced by adenine loaded.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、腎移植後に起こる腎組織の線維化の病態形成に関わる早期評価指標、さらには腎線維化抑制関連分子の同定に繋がる基礎研究の位置付けと考えている。今後は、抽出されたこれら候補分子の腎線維化早期指標としての可能性について動物実験にて確認すると共に、並行して腎移植患者の尿・血液・組織検体から得られる臨床データを解析することにより当該分子群の意義を明確化さらに検証することにより臨床応用への基盤研究に寄与することが期待できる。

Report

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

    (26 results)

All 2023 2022 2021

All Journal Article (26 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 26 results,  Open Access: 19 results)

  • [Journal Article] Irradiation plus myeloid-derived suppressor cell-targeted therapy for overcoming treatment resistance in immunologically cold urothelial carcinoma2023

    • Author(s)
      Yamamoto Shoma、Kato Minoru、Takeyama Yuji、Azuma Yukari、Yukimatsu Nao、Hirayama Yukiyoshi、Otoshi Taiyo、Yamasaki Takeshi、Fujioka Masaki、Gi Min、Wanibuchi Hideki、Uchida Junji
    • Journal Title

      British Journal of Cancer

      Volume: . Issue: 12 Pages: 1-9

    • DOI

      10.1038/s41416-023-02244-8

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kidney transplantation for a transgender male.2023

    • Author(s)
      Kosoku A, Iwai T, Masuda H, Kabei K, Nishide S, Uchida J
    • Journal Title

      CEN Case Rep

      Volume: 12 Issue: 4 Pages: 352-356

    • DOI

      10.1007/s13730-023-00773-y

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development and nationwide validation of kidney graft injury markers using urinary exosomes and microvesicles.2023

    • Author(s)
      Harada H, Fukuzawa N, Abe T, Imamura R, Masaki N, Fujiyama N, Sato S, Hatakeyama S, Nishimura K, Kishikawa H, Iwami D, Hotta K, Miura M, Ide K, Nakamura M, Kosoku A, Uchida J, Murakami T, Tsuji T.
    • Journal Title

      BMC Nephrol

      Volume: 24 Issue: 1

    • DOI

      10.1186/s12882-023-03189-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Frailty and sarcopenia in older kidney transplant recipients: a cross-sectional study.2023

    • Author(s)
      Kosoku A, Iwai T, Kabei K, Nishide S, Machida Y, Uchida J
    • Journal Title

      Eur Geriatr Med

      Volume: 14 Issue: 4 Pages: 861-868

    • DOI

      10.1007/s41999-023-00803-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Case of Bariatric Surgery for a Japanese Kidney Transplant Recipient With Diabetes Mellitus: A Case Report.2023

    • Author(s)
      Kabei K, Iwai T, Kosoku A, Nishide S, Iguchi K, Machida Y, Naganuma T, Uchida J.
    • Journal Title

      Transplant Proc.

      Volume: 55 Issue: 8 Pages: 1910-1912

    • DOI

      10.1016/j.transproceed.2023.07.002

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Male Renal Transplant Recipients' Experiences From Their Wives' Pregnancy and Childbirth.2023

    • Author(s)
      Yoshikawa Y, Maeda K, Kosoku A, Uchida J.
    • Journal Title

      Transplant Proc

      Volume: 55 Issue: 9 Pages: 2046-2052

    • DOI

      10.1016/j.transproceed.2023.07.033

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety Profile of the Concomitant Use of Atorvastatin and Cyclosporine in Renal Transplant Recipients.2023

    • Author(s)
      Harabayashi R, Takahashi M, Takahashi K, Sugimoto T, Uchida J, Nakamura Y, Nagayama K.
    • Journal Title

      Pharmazie

      Volume: 78 Pages: 47-50

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kidney Transplantation After Renal Transcatheter Arterial Embolization for Cyst Infection in a Hemodialysis Patient With Autosomal Dominant Polycystic Kidney Disease2023

    • Author(s)
      Iguchi K, Iwai T, Kosoku A, Nishide S, Kabei K, Kumada N, Uchida J
    • Journal Title

      Transplant Proc

      Volume: 55 Issue: 4 Pages: 1065-1067

    • DOI

      10.1016/j.transproceed.2023.03.055

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reliability and Validity of the Japanese Version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale in Kidney Transplant Recipients2023

    • Author(s)
      Kosoku Akihiro、Iwai Tomoaki、Masuda Hiroo、Kabei Kazuya、Nishide Shunji、Maeda Keiko、Yoshikawa Yuki、Nakamura Yasutaka、De Geest Sabina、Uchida Junji
    • Journal Title

      Transplantation Direct

      Volume: 9 Issue: 3 Pages: e1457-e1457

    • DOI

      10.1097/txd.0000000000001457

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Case of Metastatic Urothelial Carcinoma with Pseudoprogression of Liver Metastasis during the Treatment with Pembrolizumab2022

    • Author(s)
      Masuda H, Kato M, Yoshiuchi H, Yukimatsu N, Hirayama Y, Otoshi T, Yamasaki T, Kuratsukuri K, Uchida J.
    • Journal Title

      泌尿器科紀要

      Volume: 68 Issue: 4 Pages: 117-121

    • DOI

      10.14989/ActaUrolJap_68_4_117

    • ISSN
      0018-1994
    • Year and Date
      2022-04-30
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic ureteroneocystostomy for iatrogenic ureterovaginal fistula after modified radical hysterectomy: A case report.2022

    • Author(s)
      Machida Y, Yoshiuchi H, Kitano Y, Kamizuru M, Uchida J
    • Journal Title

      Urol Case Rep

      Volume: 44 Pages: 102144-102144

    • DOI

      10.1016/j.eucr.2022.102144

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influence of protein intake on the changes in skeletal muscle mass after kidney transplantation.2022

    • Author(s)
      Kosoku A, Iwai T, Ishihara T, Kabei K, Nishide S, Maeda K, Hanayama Y, Ishimura E, Uchida J
    • Journal Title

      Clin Nutr.

      Volume: 41 Issue: 9 Pages: 1881-1888

    • DOI

      10.1016/j.clnu.2022.07.028

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] The carbonic anhydrase inhibitor acetazolamide inhibits urinary bladder cancers via suppression of β-catenin signaling.2022

    • Author(s)
      Matsue T, Gi M, Shiota M, Tachibana H, Suzuki S, Fujioka M, Kakehashi A, Yamamoto T, Kato M, Uchida J, Wanibuchi H.
    • Journal Title

      Cancer Sci.

      Volume: 113 Issue: 8 Pages: 2642-2653

    • DOI

      10.1111/cas.15467

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel Technique for Hand-Assisted Laparoscopic Nephrectomy for Advanced Renal Cell Carcinoma with Renal Vein and Inferior Vena Cava Thrombi: Three Case Reports.2022

    • Author(s)
      Machida Y, Yoshiuchi H, Kitano Y, Kuroki Y, Kamizuru M, Uchida J.
    • Journal Title

      Case Rep Urol.

      Volume: 28 Pages: 1-4

    • DOI

      10.1155/2022/8177947

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Successful case of olaparib treatment for castration-resistant prostate cancer with multiple DNA repair gene mutations: Use of comprehensive genome profiling for treatment-refractory cases.2022

    • Author(s)
      Hirayama Y, Kato M, Kimura K, Otoshi T, Yamasaki T, Uchida J
    • Journal Title

      Urol Case Rep

      Volume: 45 Pages: 102210-102210

    • DOI

      10.1016/j.eucr.2022.102210

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Intranodal Lymphangiography for Chyluria2022

    • Author(s)
      Kosoku Akihiro、Iwai Tomoaki、Jogo Atsushi、Yamamoto Akira、Uchida Junji
    • Journal Title

      Journal of Vascular and Interventional Radiology

      Volume: 33 Issue: 3 Pages: 357-357

    • DOI

      10.1016/j.jvir.2021.12.014

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Experience With the Use of a Novel Agent, Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, for Posttransplant Anemia in Renal Transplant Recipients: A Case Report2022

    • Author(s)
      Naganuma Toshihide、Iwai Tomoaki、Takemoto Yoshiaki、Uchida Junji
    • Journal Title

      Transplantation Proceedings

      Volume: 54 Issue: 2 Pages: 544-548

    • DOI

      10.1016/j.transproceed.2021.10.022

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hyperpolypharmacy and Frailty in Kidney Transplant Recipients2022

    • Author(s)
      Kosoku Akihiro、Iwai Tomoaki、Kabei Kazuya、Nishide Shunji、Maeda Keiko、Kumada Norihiko、Uchida Junji
    • Journal Title

      Transplantation Proceedings

      Volume: 54 Issue: 2 Pages: 367-373

    • DOI

      10.1016/j.transproceed.2021.11.026

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Outcomes of Everolimus With Reduced-Dose Tacrolimus vs Mycophenolate Mofetil With Standard-Dose Tacrolimus in De Novo ABO-Incompatible Kidney Transplant Recipients: 1-Year Follow-up2022

    • Author(s)
      Kosoku Akihiro、Iwai Tomoaki、Uchida Junji
    • Journal Title

      Transplantation Proceedings

      Volume: 54 Issue: 2 Pages: 293-298

    • DOI

      10.1016/j.transproceed.2021.08.062

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Change in Muscle Mass Among Kidney Transplant Recipients: A Prospective Cohort Study2022

    • Author(s)
      Kosoku Akihiro、Ishihara Takuma、Iwai Tomoaki、Nishide Shunji、Kabei Kazuya、Maeda Keiko、Kumada Norihiko、Uchida Junji
    • Journal Title

      Transplantation Proceedings

      Volume: 54 Issue: 2 Pages: 346-350

    • DOI

      10.1016/j.transproceed.2021.08.064

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A retrospective study on optimal number of cycles of the first-line platinum-based chemotherapy for metastatic urothelial carcinoma2021

    • Author(s)
      Yamamoto Shoma、Kato Minoru、Takeyama Yuji、Yukimatsu Nao、Hirayama Yukiyoshi、Otoshi Taiyo、Yamasaki Takeshi、Kuratsukuri Katsuyuki、Uchida Junji
    • Journal Title

      Urologic Oncology: Seminars and Original Investigations

      Volume: - Issue: 5 Pages: 194.e7-194.e14

    • DOI

      10.1016/j.urolonc.2021.10.013

    • Related Report
      2022 Research-status Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of the objective response to and number of cycles of platinum‐based first‐line chemotherapy for metastatic urothelial carcinoma on overall survival of patients treated with pembrolizumab2021

    • Author(s)
      Kato Minoru、Kobayashi Takashi、Japan Urological Oncology Group
    • Journal Title

      International Journal of Urology

      Volume: 28 Issue: 12 Pages: 1261-1267

    • DOI

      10.1111/iju.14686

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dissociation of Glycated Albumin and HbA1c Is Associated With a Decline of Glomerular Filtration Rate as Evaluated by Inulin Clearance2021

    • Author(s)
      Tsuda Akihiro、Mori Katsuhito、Nakatani Shinya、Machiba Yuri、Uedono Hideki、Kurajoh Masafumi、Yamada Shinsuke、Morioka Tomoaki、Inaba Masaaki、Ishimura Eiji、Uchida Junji、Emoto Masanori
    • Journal Title

      Diabetes Care

      Volume: 44 Issue: 11 Pages: e188-e189

    • DOI

      10.2337/dc21-1218

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of stroke history on the presence of cerebral microbleeds in hemodialysis patients2021

    • Author(s)
      Naganuma Toshihide、Kabata Daijiro、Takemoto Yoshiaki、Uchida Junji、Shintani Ayumi
    • Journal Title

      BMC Neurology

      Volume: 21 Issue: 1

    • DOI

      10.1186/s12883-021-02320-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antiplatelet therapy and future intracerebral hemorrhage in hemodialysis patients with cerebral microbleeds2021

    • Author(s)
      Naganuma Toshihide、Kabata Daijiro、Takemoto Yoshiaki、Uchida Junji、Shintani Ayumi
    • Journal Title

      Journal of Clinical Neuroscience

      Volume: 90 Pages: 155-160

    • DOI

      10.1016/j.jocn.2021.05.068

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of primary retroperitoneal amyloidoma resected laparoscopically2021

    • Author(s)
      Kuroki Yoshikazu、Kimura Kaoru、Harimoto Koji、Nishikawa Keiichiro、Hosaka Naoki、Uchida Junji
    • Journal Title

      Urology Case Reports

      Volume: 38 Pages: 101711-101711

    • DOI

      10.1016/j.eucr.2021.101711

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

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

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