尿路結石マトリックス蛋白オステオポンチンを標的としたマクロファージ貪食機序の解明

2021 Fiscal Year Research-status Report

• Project/Area Number: 20K09562
• Research Institution: Nagoya City University
• Principal Investigator: 岡田 淳志 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (70444966)
• Co-Investigator(Kenkyū-buntansha): 田口 和己 名古屋市立大学, 医薬学総合研究院(医学), 講師 (00595184) ; 郡 健二郎 名古屋市立大学, その他部局等, 学長 (30122047) ; 安藤 亮介 名古屋市立大学, 医薬学総合研究院(医学), 教授 (30381867) ; 松永 民秀 名古屋市立大学, 医薬学総合研究院(薬学), 教授 (40209581) ; 安井 孝周 名古屋市立大学, 医薬学総合研究院(医学), 教授 (40326153) ; 濱本 周造 名古屋市立大学, 医薬学総合研究院(医学), 講師 (80551267)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 尿路結石 / マクロファージ / 貪食 / 結晶溶解 / オステオポンチン / 化合物ライブラリー

Outline of Annual Research Achievements

[1] 培養Mφを用いたM1/M2マクロファージ結晶貪食解析法の確立
① 培養Mφを用いたM1/M2誘導による貪食解析：昨年度は貪食能の定量化の確立を行い、IFN-γ・IL-4投与によるf-COM結晶貪食率の差異を確認できなかった。この理由として、培養MφのM1/M2への分化を期待した研究方針であったと認識し、本研究はこの段階で中止として全般的に化合物ライブラリー研究へと移行した。
② 既存薬ライブラリーによる貪食能の亢進薬の選出：昨年度2600種類の既存薬ライブラリーFDA-approved Drug Library (384-well)-L1300の導入を決定し、抽出した約800種類の薬剤に関し貪食解析を開始した。IncuCyteハイスループット生細胞解析システムで、細胞面積とCOM面積を測定し、総COM残量 (crystal remaining amount; CRA)を算出した。すべての薬剤について、3-5回同じ条件で実験を行い、CRAを測定した。現在、COM結晶の貪食を有意に変化させる薬剤について抽出中である。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

専属研究者を雇用し、IncuCyteを用いた研究条件の設定を十分に行ったため、その後800種類の薬剤に関する貪食解析を比較的スムーズに完了できた。またその後の再検についても順調に進んでいる。
また、次の候補約800種類についても導入を進めている。

Strategy for Future Research Activity

[1]既存薬ライブラリーによる貪食能変化についての解析を継続する。
[2]OPN欠損マウスを用いたマクロファージ分布解析・貪食解析については、OPN欠損マウスの骨髄由来Mφを用いた貪食解析を開始していく。
[3] ヒトiPS細胞由来Mφを用いた腎結石貪食解析については、ヒトiPS細胞由来MφのM1/M2への分化誘導とf-COM結晶貪食解析、ならびにヒトiPS細胞由来Mφの腎結石の貪食解析と貪食促進薬の効果判定を行っていく。

Causes of Carryover

培養Mφを用いたM1/M2マクロファージ結晶貪食解析法の確立をする計画であった。計画自体は順調な滑り出しであったがCOVID-19による通常の医療業務が大幅に変更となり、予定してていた研究を進めることができなかった。また国際・国内学会出張も計画していたが、出張することもできなかった。このため次年度使用が生じた。最終年度として、「オステオポンチン(OPN)欠損マウスを用いたマクロファージ分布解析・貪食解析」を行いたい。

Research Products

• [Journal Article] Independent and interactive effects of kidney stone formation and conventional risk factors for chronic kidney disease: a follow-up study of Japanese men (2021)
  • Author(s): Ando Ryosuke、Nagaya Teruo、Suzuki Sadao、Takahashi Hidekatsu、Kawai Makoto、Taguchi Kazumi、Hamamoto Shuzo、Okada Atsushi、Yasui Takahiro
  • Journal Title: International Urology and Nephrology Volume: 53 Pages: 1081-1087
  • DOI: 10.1007/s11255-021-02803-z
  • Peer Reviewed
• [Journal Article] Comparison of antegrade and retrograde ureterolithotripsy for proximal ureteral stones: a systematic review and meta-analysis (2021)
  • Author(s): Taguchi Kazumi、Hamamoto Shuzo、Osaga Satoshi、Sugino Teruaki、Unno Rei、Ando Ryosuke、Okada Atsushi、Yasui Takahiro
  • Journal Title: Translational Andrology and Urology Volume: 10 Pages: 1179～1191
  • DOI: 10.21037/tau-20-1296
  • Peer Reviewed / Open Access
• [Journal Article] Robot‐assisted fluoroscopy‐guided renal puncture for endoscopic combined intrarenal surgery: a pilot single‐centre clinical trial (2021)
  • Author(s): Taguchi Kazumi、Hamamoto Shuzo、Kato Taiki、Iwatsuki Shoichiro、Etani Toshiki、Okada Atsushi、Yasui Takahiro
  • Journal Title: BJU International Volume: 127 Pages: 307～310
  • DOI: 10.1111/bju.15291
  • Peer Reviewed / Open Access
• [Journal Article] Macrophage Function in Calcium Oxalate Kidney Stone Formation: A Systematic Review of Literature (2021)
  • Author(s): Taguchi Kazumi、Okada Atsushi、Unno Rei、Hamamoto Shuzo、Yasui Takahiro
  • Journal Title: Frontiers in Immunology Volume: 12 Pages: 673690
  • DOI: 10.3389/fimmu.2021.673690
  • Peer Reviewed / Open Access
• [Journal Article] Ureteroscopy‐assisted puncture for ultrasonography‐guided renal access significantly improves overall treatment outcomes in endoscopic combined intrarenal surgery (2021)
  • Author(s): Taguchi Kazumi、Yamashita Shimpei、Hamamoto Shuzo、Deguchi Ryusuke、Kawase Kengo、Okada Tomoki、Kato Taiki、Ando Ryosuke、Okada Atsushi、Kohjimoto Yasuo、Hara Isao、Yasui Takahiro
  • Journal Title: International Journal of Urology Volume: 28 Pages: 913～919
  • DOI: 10.1111/iju.14603
  • Peer Reviewed
• [Journal Article] Comparison of the safety and efficacy between the prone split‐leg and Galdakao‐modified supine Valdivia positions during endoscopic combined intrarenal surgery: A multi‐institutional analysis (2021)
  • Author(s): Hamamoto Shuzo、Okada Shinsuke、Inoue Takaaki、Taguchi Kazumi、Kawase Kengo、Okada Tomoki、Chaya Ryosuke、Hattori Tatsuya、Okada Atsushi、Matsuda Tadashi、Yasui Takahiro、the SMART Study Group
  • Journal Title: International Journal of Urology Volume: 28 Pages: 1129～1135
  • DOI: 10.1111/iju.14655
  • Peer Reviewed
• [Journal Article] Validation of the Japanese Version of The Wisconsin Stone Quality of Life Questionnaire: Results from SMART Study Group (2021)
  • Author(s): Okada Tomoki、Hamamoto Shuzo、Taguchi Kazumi、Okada Shinsuke、Inoue Takaaki、Fukuta Hidekatsu、Chew Ben H.、Penniston Kristina、Okada Atsushi、Yasui Takahiro
  • Journal Title: Journal of Endourology Volume: 35 Pages: 1852～1856
  • DOI: 10.1089/end.2021.0292
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Bisphosphonate Use May Reduce the Risk of Urolithiasis in Astronauts on Long‐Term Spaceflights (2021)
  • Author(s): Okada Atsushi、Matsumoto Toshio、Ohshima Hiroshi、Isomura Tatsuya、Koga Tadashi、Yasui Takahiro、Kohri Kenjiro、LeBlanc Adrian、Spector Elisabeth、Jones Jeffrey、Shackelford Linda、Sibonga Jean
  • Journal Title: JBMR Plus Volume: 6 Pages: 184-189
  • DOI: 10.1002/jbm4.10550
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel approach in creating nephrostomy using a double-lumen access sheath during endoscopic combined intrarenal surgery (2021)
  • Author(s): Unno Rei、Taguchi Kazumi、Hamamoto Shuzo、Hattori Tatsuya、Kawase Kengo、Okada Tomoki、Chaya Ryosuke、Tanaka Yutaro、Sugino Teruaki、Kato Taiki、Etani Toshiki、Ando Ryosuke、Okada Atsushi、Yasui Takahiro
  • Journal Title: Translational Andrology and Urology Volume: 10 Pages: 4181～4191
  • DOI: 10.21037/tau-21-611
  • Peer Reviewed
• [Presentation] THE USEFULNESS OF ULTRASOUND MONITORING DURING EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY (2021)
  • Author(s): Isogai Masahiko, Hamamoto Shuzo, Hattori Tatsuya, Chaya Ryosuke, Okada Tomoki, Kawase Kengo, Kato Taiki, Taguchi Kazumi, Kobayashi Takahiro, Okada Atsushi, Umemoto Yukihiro, Tozawa Keiichi, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] STONE FORMATION BY ANALYSIS OF UROFLOW DYNAMICS IN THE RENAL PELVIS (2021)
  • Author(s): Kawase Kengo,Hamamoto Shuzo, Hattori Shota, chaya Ryosuke, Okada Tomoki, Tanaka Yutaro, Sugino Takeru, Unno Rei, Taguchi Kazumi, Ando Ryosuke, Okada Atsushi, Nakamura Masanori, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] THE MECHANISM OF KIDNEY STONE SUPPRESSION BY PROLINE HYDROXYLASE INHIBITOR ADMINISTRATION (2021)
  • Author(s): Kawase Kengo, Hamamoto Shuzo, Hattori Tatsuya, Okada Tomoki, Tanaka Yutaro, Sugino Takeru, Unno Rei, Taguchi Kazumi, Ando Ryosuke, Okada Atsushi, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] FATTY ACID BINDING PROTEIN 4 ATTENUATES MACROPHAGE AND TUBULAR CELLS CRYSTAL PHAGOCYTOSIS TO DRIVE RENAL CALCIUM OXALATE STONE DEVELOPMENT (2021)
  • Author(s): Taguchi Kazumi, Unno Rei, Sugino Teruaki, Kawase Kengo, Heiko Yang, Hamamoto Shuzo, Okada Atsushi, Marshall Stoller, Yasui Takahiro, Tom Chi,
  • Organizer: American Urological Association Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] COMPARISON OF SAFETY AND EFFICACY BETWEEN PRONE SPLIT-LEG AND MODIFIED SUPINE VALDIVIA POSITIONS IN ENDOSCOPIC COMBINED INTRARENAL SURGERY (ECIRS): A MULTI-INSTITUTIONAL ANALYSIS (2021)
  • Author(s): Hamamoto Shuzo, Okada Shinsuke, Inoue Takaaki, Taguchi Kazumi, Kawase Kengo, Okada Tomoki, Chaya Ryosuke, Hattori Tatsuya, Okada Atsushi, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] URETEROSCOPY-ASSISTED VERSUS CONVENTIONAL ULTRASOUND-GUIDED RENAL ACCESS FOR MINIATURIZED ENDOSCOPIC COMBINED INTRARENAL SURGERY: A MULTICENTER COMPARATIVE STUDY (2021)
  • Author(s): Taguchi Kazumi, Yamashita Shimpei, Hamamoto Shuzo, Deguchi Ryusuke, Kawase Kengo, Okada Tomoki, Unno Rei, Kato Taiki, Ando Ryosuke, Okada Atsushi,Kohjimoto Yasuo, Hara Isao, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] BROWN ADIPOCYTES COULD PREVENT URINARY STONES IN THE HUMAN BODY (2021)
  • Author(s): Sugino Teruaki, Taguchi Kazumi, Unno Rei, Hamamoto Shuzo, Ando Ryosuke, Okada Atsushi, Yasui Takahiro
  • Organizer: American Urological Association Annual Meeting 2021
  • Int'l Joint Research
• [Presentation] ROBOTIC-ASSISTED FLUOROSCOPIC-GUIDED RENAL PUNCTURE HAS COMPARABLE SURGICAL OUTCOMES WITH ULTRASOUND-GUIDED IN ENDOSCOPIC COMBINED INTRARENAL SURGERY: A RANDOMIZED CONTROLLED TRIAL (2021)
  • Author(s): Taguchi Kazumi, Hamamoto Shuzo, Sue Yasuhito, Kobayakawa Yuki, Hattori Tatsuya, Okada Tomoki, Chaya Ryosuke, Sugino Teruaki, Kato Taiki, Okada Atsushi, Yasui Takahiro
  • Organizer: Taguchi Kazumi, Hamamoto Shuzo, Sue Yasuhito, Kobayakawa Yuki, Hattori Tatsuya, Okada Tomoki, Chaya Ryosuke, Sugino Teruaki, Kato Taiki, Okada Atsushi, Yasui Takahiro
  • Int'l Joint Research
• [Presentation] Basic research toward dissolution therapy for calcium oxalate stones (2021)
  • Author(s): Okada Atsushi, Okada Tomoki, Sugino Teruaki, Unno Rei, Taguchi Kazumi, Hamamoto Shuzo, Ando Ryosuke, Tozawa Keiichi, Kohri Kenjiro, Yasui Takahiro
  • Organizer: THE 37th KOREA-JAPAN UROLOGICAL CONGRESS
  • Int'l Joint Research / Invited
• [Presentation] The impact protein mapping in human kidney stone by multiple multifaceted structure analysis (2021)
  • Author(s): Tanaka Yutaro, Okada Atsushi, Maruyama Mihoko, Tajiri Rie, Sugino Teruaki, Taguchi Kazumi, Hamamoto Shuzo, Mori Yusuke, Kohri Kenjiro, Yasui Takahiro
  • Organizer: THE 37th KOREA-JAPAN UROLOGICAL CONGRESS
  • Int'l Joint Research