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
Project/Area Number |
20K09562
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56030:Urology-related
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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)
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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)
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Project Period (FY) |
2020-04-01 – 2024-03-31
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Project Status |
Granted (Fiscal Year 2022)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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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 / iPS細胞 / ノックアウトマウス |
Outline of Research at the Start |
[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、② 既存薬ライブラリーによる貪食能の亢進薬の選出 [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:③ OPN添加f-COM結晶のMφ貪食試験、④ OPN欠損マウスの腎結晶・Mφを用いた貪食解析 [3] ヒトiPS細胞由来Mφを用いた腎結石貪食解析:⑤ 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、⑥ 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
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Outline of Annual Research Achievements |
[1] 培養Mφ・iPS細胞由来Mφによる結晶貪食モデルの確立 ① 培養Mφを用いたM1/M2誘導による貪食解析:完了している。② 既存薬ライブラリーによる貪食能の亢進薬の選出:既存薬ライブラリーFDA-approved Drug Library (384-well)-L1300の約800種類の薬剤に関し貪食解析を完了した。現在追加で800種類の解析を行っている。一次スクリーニングn=3、二次スクリーニングn=10で行い、薬剤と結晶のみでの単独実験で直接作用を持つものを除外した。現在追加800種類の2次スクリーニングが終了しつつある。 [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 ③ OPN添加f-COM結晶のMφ貪食試験:[1]①研究が完了していないため、着手していない。④ OPN欠損マウスの腎結晶・Mφを用いた貪食解析:OPNノックアウトマウスと野生型マウスから骨髄Mφ(Bone marrow-derived macrophage; BMDM)を採取し、COM結晶を暴露した。OPN-/-BMDMはOPNが有意に抑制されていたが、COM結晶の接着率は、OPN-/-型がOPN+/+型よりも有意に多かった。OPN-/-BMDMのIntgavとIntgb3の発現は、OPN+/+と比較してそれぞれ0.80倍(p=0.41), 1.61倍(p<1.61)であった。 [3] ヒトiPS細胞由来Mφを用いた腎結石貪食解析 ⑤ 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:結石患者・健常者由来iPS細胞MφからM1/M2に分化させることに成功した。また[1]の手法を用いてf-COM結晶を貪食することを確認できた。⑥ 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:②の薬剤スクリーニング中であり、開始できていない。
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
[1]IncuCyteによる正確な解析方法を確立し、既存薬ライブラリー研究を完了しつつある。 [2]またOPN-KOマウス研究も、骨髄由来Mφの結晶付着解析について確立し、発現解析も進みつつある。 [3]iPS細胞由来Mφの分化が成功し、結晶貪食を確認できた。
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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]引き続き OPN欠損マウス骨髄由来マクロファージの貪食解析を進める。 [3] ヒトiPS細胞由来Mφを用いた腎結石貪食解析として、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[1]で選出した薬剤の効果を確認する研究を行う。
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Report
(3 results)
Research Products
(86 results)
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[Journal Article] A Multicenter, Prospective, Non-randomized Study Evaluating Surgical Hand Preparation between Double-Gloving and Single-Gloving for Preventing Postoperative Infection in Robotic and Laparoscopic Minimally Invasive Surgeries2022
Author(s)
Nagai Takashi, Taguchi Kazumi, Isobe Teruki, Matsuyama Nayuka, Hattori Tatsuya, Unno Rei, Kato Taiki, Etani Toshiki, Hamakawa Takashi, Fujii Yasuhiro, Ikegami Yosuke, Kamiya Hiroyuki, Hamamoto Shuzo, Nakane Akihiro, Ando Ryosuke, Maruyama Tetsuji, Okada Atsushi, Kawai Noriyasu, Yasui Takahiro
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Journal Title
Urol J
Volume: 20(2)
Pages: 109-115
Related Report
Peer Reviewed
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[Journal Article] Taguchi KaRobot-assisted fluoroscopy-guided renal puncture for endoscopic combined intrarenal surgery: a pilot single-centre clinical trialzumi, Hamamoto Shuzo, Kato Taiki, Iwatsuki Shoichiro, Etani Toshiki, Okada Atsushi, Yasui Takahiro2021
Author(s)
Taguchi K, Hamamoto S, Kato T, Iwatsuki S, Etani T, Okada A, Yasui T
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Journal Title
BJU International
Volume: 127
Issue: 3
Pages: 307-310
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prospective evaluation and classification of endoscopic findings for ureteral calculi2020
Author(s)
Hamamoto Shuzo, Okada Shinsuke, Inoue Takaaki, Sugino Teruaki, Unno Rei, Taguchi Kazumi, Ando Ryosuke, Okada Atsushi, Miura Hiroyasu, Matsuda Tadashi, Yasui Takahiro
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Journal Title
SCIENTIFIC REPORTS
Volume: 10
Issue: 1
Pages: 12292-12292
DOI
Related Report
Peer Reviewed
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[Presentation] Effectiveness of Virtual Reality simulation of renal puncture for endoscopic-combined intrarenal surgery2022
Author(s)
Okada Atsushi, Ohashi Kazuya, Noda Yusuke, Okada Tomoki, Chaya Ryosuke, Kawase Kengo, Kato Taiki, Taguchi Kazumi, Hamamoto Shuzo, Tozawa Keiichi, Kohri Kenjiro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2022
Related Report
Int'l Joint Research
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[Presentation] Discovery of drugs that promote the phagocytic ability of macrophages to calcium oxalate crystals using the FDA-approved Drug Library2022
Author(s)
Okada Atsushi, Takase Hiroshi, Isogai Masahiko, Okada Tomoki, Hattori Tatsuya, Chaya Ryosuke, Kawase Kengo, Tanaka Yutaro, Kato Taiki, Sugino Teruaki, Unno Rei, Taguchi Kazumi, Hamamoto Shuzo, Ando Ryosuke, Hashita Tadahiro, Tozawa Keiichi, Matsunaga Tamihide, Kohri Kenjiro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2022
Related Report
Int'l Joint Research
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[Presentation] THE USEFULNESS OF ULTRASOUND MONITORING DURING EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY2021
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
Related Report
Int'l Joint Research
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[Presentation] STONE FORMATION BY ANALYSIS OF UROFLOW DYNAMICS IN THE RENAL PELVIS2021
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
Related Report
Int'l Joint Research
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[Presentation] THE MECHANISM OF KIDNEY STONE SUPPRESSION BY PROLINE HYDROXYLASE INHIBITOR ADMINISTRATION2021
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
Related Report
Int'l Joint Research
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[Presentation] FATTY ACID BINDING PROTEIN 4 ATTENUATES MACROPHAGE AND TUBULAR CELLS CRYSTAL PHAGOCYTOSIS TO DRIVE RENAL CALCIUM OXALATE STONE DEVELOPMENT2021
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
Related Report
Int'l Joint Research
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[Presentation] URETEROSCOPY-ASSISTED VERSUS CONVENTIONAL ULTRASOUND-GUIDED RENAL ACCESS FOR MINIATURIZED ENDOSCOPIC COMBINED INTRARENAL SURGERY: A MULTICENTER COMPARATIVE STUDY2021
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
Related Report
Int'l Joint Research
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[Presentation] ROBOTIC-ASSISTED FLUOROSCOPIC-GUIDED RENAL PUNCTURE HAS COMPARABLE SURGICAL OUTCOMES WITH ULTRASOUND-GUIDED IN ENDOSCOPIC COMBINED INTRARENAL SURGERY: A RANDOMIZED CONTROLLED TRIAL2021
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
Related Report
Int'l Joint Research
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[Presentation] M2 macrophages differentiated from iPS cells have higher abilities to phagocytose and process calcium oxalate crystals than similarly induced M1 macrophages2020
Author(s)
Okada Atsushi, Aoki Hiromasa, Onozato Daichi, Kato Taiki, Takase Hiroshi, Ohshima Shigeru, Banno Rika, Taguchi Kazumi, Hashita Tadahiro, Matsunaga Tamihide, Kohri Kenjiro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Usefulness of determination of renal puncture line in ECIRS using Virtual Reality2020
Author(s)
Okada Atsushi , Noda Yusuke, Ohashi Kazuya, Okada Tomoki, Chaya Ryosuke, Kawase Kengo, Kato Taiki, Taguchi Kazumi, Hamamoto Shuzo, Hirose Yasujiro, Tozawa Keiichi, Kohri Kenjiro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Impact of insulin resistance and physical activity on kidney stone formation in the Japanese population: A prospective cohort study2020
Author(s)
Ando Ryosuke, Suzuki Sadao, Nishiyama Takeshi, Nakagawa Hiroko,Hosono Akihiro, Watanabe Miki, Yamada Tamaki, Taguchi Kazumi, Hamamoto Shuzo, Okada Atsushi, Tozawa Keiichi, Kohri Kenjiro,Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] The importance of hands-on training for flexible ureteroscope (fURS): Appropriate training as examined based on questionnaires2020
Author(s)
Hamamoto Shuzo, Okada Shinsuke, Inoue Takaaki, Okada Tomoki, Chaya Ryosuke, Kawase Kengo, Taguchi Kazumi, Okada Atsushi, Miura Hiroyasu, Matsuda Tadashi, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Prospective evaluation of endoscopic findings and analyses of the risk factors for ureteral changes during URSL2020
Author(s)
Hamamoto Shuzo, Okada Shinsuke, Inoue Takaaki, Okada Tomoki, Chaya Ryosuke, Kawase Kengo, Taguchi Kazumi, Okada Atsushi, Miura Hiroyasu, Matsuda Tadashi, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Investigation of the ideal position for endoscopic combined intrarenal surgery: Prone split-leg position vs. modified Valdivia position2020
Author(s)
Hamamoto Shuzo, Okada Shinsuke, Inoue Takaaki, Okada Tomoki, Chaya Ryosuke, Kawase Kengo, Taguchi Kazumi, Okada Atsushi, Miura Hiroyasu, Matsuda Tadashi, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Impact of preoperative ureteral stenting on endoscopic findings: A propensity score matching analysis2020
Author(s)
Hamamoto Shuzo, Okada Shinsuke, Inoue Takaaki, Okada Tomoki, Chaya Ryosuke, Kawase Kengo, Taguchi Kazumi, Okada Atsushi, Miura Hiroyasu, Matsuda Tadashi, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Fatty acid binding protein 4 drives calcification in the development of kidney stone disease2020
Author(s)
Taguchi Kazumi, Chen Ling, Hamamoto Shuzo, Sugino Teruaki, Kang Misun, Unno Rei, Benjamin A Sherer, Manint Usawachintachit, David T Tzou, Okada Atsushi, Sunita P Ho, Marshall L Stoller, Yasui Takahiro , and Thomas Chi
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Robotic-assisted fluoroscopic guidance provides more accurate and confident renal access than ultrasound guidance2020
Author(s)
Taguchi Kazumi, Okada Tomoki, Kawase Kengo, Sugino Teruaki, Tanaka Yutaro, Unno Rei, Kato Taiki, Hamamoto Shuzo, Ando Ryosuke, Okada Atsushi, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Administration of antioxidants inhibits the development of renal crystals via Keap1/Nrf2 pathway2020
Author(s)
Unno Rei, Kawase Kengo, Sugino Teruaki, Tanaka Yutaro, Taguchi Kazumi, Unno Naoko, Hamamoto Shuzo, Ando Ryosuke, Okada Atsushi, Nakane Akihiro, Kohri Kenjiro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Surgical hand hygiene and febrile urinary tract infections in endourological surgery: a single-center prospective cohort study2020
Author(s)
Unno Rei, Taguchi Kazumi, Fuji Yasuhiro, Unno Naoko, Hamamoto Shuzo, Ando Ryosuke, Okada Atsushi, Nakane Akihiro, Kamiya Hiroyuki, Kohri Kenjiro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Brown adipocytes suppress kidney stone formation via heat-producing protein, uncoupling protein 12020
Author(s)
Sugino Teruaki, Okada Atsushi, Chaya Ryosuke, Tanaka Yutaro, Unno Rei, Taguchi Kazumi, Hamamoto Shuzo, Ando Ryosuke, Mogami Tohru, Yamashita Hitoshi, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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[Presentation] Discovering spatial distribution and differential localization of protein matrix in calcium oxalate stones; A novel method of multifaceted structure analysis2020
Author(s)
Tanaka Yutaro, Okada Atsushi, Maruyama Mihoko, Tagiri Rie, Sugino Teruaki, Unno Rei, Taguchi Kazumi, Hamamoto Shuzo, Ando Ryosuke, Yoshimura Masashi, Mori Yusuke, Kohri Kenjiro, Yasui Takahiro
Organizer
American Urological Association Annual Meeting 2020
Related Report
Int'l Joint Research
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