The development of a specific anti-OPN antibody which contributes to to the remarkable inhibition of early stage of renal crystal formation

• Project/Area Number: 24791663
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: SHUZO Hamamoto 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (80551267)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 腎結石 / オステオポンチン / 尿路結石 / 抗体治療 / サル / 動物実験

Outline of Final Research Achievements

Osteopontin plays a crucial role in the formation of renal calcium crystals, which are primarily induced by renal tubular cell injury, especially mitochondrial damage. We have previously shown that the impaired RGD sequence of osteopontin inhibits renal crystal formation by using OPN-transgenic mice and OPN-knockout mice. Here, we investigated the effects of an anti-murine osteopontin antibody (35B6-Ab) that specifically reacts with the 162SLAYGLR168 sequence, which is exposed by thrombin cleavage and is located adjacent to the RGD sequence, on renal crystal formation. We conclude that thrombin-cleaved osteopontin plays an important role in formation of renal calcium crystals and that 35B6-Ab contributes to the remarkable inhibition of early-stage renal crystal formation by preventing renal tubular cell injury and crystal-cell attachment.

Research Products

• [Journal Article] Efficacy of endoscopic combined intrarenal surgery in the prone split-leg position for staghorn calculi. (2015)
  • Author(s): Hamamoto S, Yasui T, Okada A, Koiwa S, Taguchi K, Itoh Y, Kawai N, Hashimoto Y, Tozawa K, Kohri K.
  • Journal Title: J Endourol Volume: 29 Issue: 1 Pages: 19-24
  • DOI: 10.1089/end.2014.0372
  • Peer Reviewed
• [Journal Article] Colony-StimulatingFactor-1 Signaling Suppresses Renal Crystal Formation. (2015)
  • Author(s): Taguchi Kazumi, Okada Atsushi, Kitamura Hiroshi, Yasui Takahiro, Naiki Taku, Hamamoto Shuzo, Ando Ryosuke, Mizuno Kentaro, Kawai Noriyasu, Tozawa Keiichi, Asano Kenichi, Tanaka Masato, Miyoshi Ichiro, Kohri Kenjiro
  • Journal Title: Journal of the American Society of Nephrology Volume: 25 Issue: 8 Pages: 1680-1697
  • DOI: 10.1681/asn.2013060675
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Developments in the technique of endoscopic combined intrarenal surgery in the prone split-leg position. (2014)
  • Author(s): Shuzo Hamamoto, Takahiro Yasui, Atsushi Okada, Mitsuru Takeuchi, Kazumi Taguchi, Yuta Shibamoto, Yutaka Iwase, Noriyasu Kawai, Keiichi Tozawa, Kohri Kenjiro
  • Journal Title: Urology Volume: 84 Issue: 3 Pages: 565-570
  • DOI: 10.1016/j.urology.2014.04.020
  • Peer Reviewed / Open Access
• [Journal Article] Increased crystal-cell interaction in vitro under co-culture of renal tubular cells and adipocytes by in vitro co-culture paracrine systems simulating metabolic syndrome. (2014)
  • Author(s): Ichikawa J, Okada A, Taguchi K, Fujii Y, Zuo L, Niimi K, Hamamoto S, Kubota Y, Umemoto Y, Itoh Y, Yasui T, Kawai N, Tozawa K, Kohri K.
  • Journal Title: Urolithiasis. Volume: 42 Issue: 1 Pages: 17-28
  • DOI: 10.1007/s00240-013-0612-5
  • Peer Reviewed
• [Journal Article] Oxygen nano-bubble water reduces calcium oxalate deposits and tubular cell injury in ethylene glycol-treated rat kidney. (2013)
  • Author(s): Hirose Y, Yasui T, Taguchi K, Fujii Y, Niimi K, Hamamoto S, Okada A, Kubota Y, Kawai N, Itoh Y, Tozawa K, Sasaki S, Kohri K.
  • Journal Title: Urolithiasis. Volume: 41 Issue: 4 Pages: 279-294
  • DOI: 10.1007/s00240-013-0576-5
  • Peer Reviewed
• [Journal Article] A replication study for three nephrolithiasis loci at 5q35.3, 7p14.3 and 13q14.1 in the Japanese population (2013)
  • Author(s): Yasui T, Okada A, Urabe Y, Usami M, Mizuno K, Kubota Y, Tozawa K, Sasaki S, Higashi Y, Sato Y, Kubo M, Nakamura Y, Matsuda K, Kohri K
  • Journal Title: J Hum Genet Volume: 58 Issue: 9 Pages: 588-93
  • DOI: 10.1038/jhg.2013.59
  • NAID: 10031195294
  • Peer Reviewed
• [Journal Article] Macrophage-derived cytokines and chemokines may be novel markers to predict calcium oxalate stone formation in humans. (2013)
  • Author(s): Okada Atsushi, Yasui Takahiro, Taguchi Kazumi, Ito Yasuhiko, Hirose Yasuhiko, Fujii Yasuhiro, Niimi Kazuhiro, Usami Masayuki, Kobayashi Takahiro, Hamamoto Shuzo, Hirose Masahito, Itoh Yasunori, Tozawa Keiichi, Kohri Kenjiro
  • Journal Title: European Urology Supplements Volume: 12 Pages: 60-60
• [Journal Article] The technique of endoscopic combined intrarenal surgery in the prone splint-leg position: Prone position is suitable for simultaneous operation of flexible ureteroscopy and mini-percutaneous nephrolithotomy (2013)
  • Author(s): Hamamoto Shuzo, Yasui Takahiro, Koiwa Satoshi, Isero Tetsuya, Kamiya Hiroyuki, Okada Atsushi, Taguchi Kazumi, Hashimoto Yoshihiro, Tozawa Keiichi, Iwase Yutaka, Kohri Kenjiro
  • Journal Title: European Urology Supplements Volume: 12 Pages: 68-68
• [Journal Article] Efficacy of retroperitoneal laparoscopic ureterolithotomy for the treatment of large proximal ureteric stones and its impact on renal function. (2013)
  • Author(s): Yasui T, Okada A, Hamamoto S, Taguchi K, Ando R, Mizuno K, Itoh Y, Tozawa K, Hayashi Y, Kohri K.
  • Journal Title: Springerplus. Volume: 2 Issue: 1 Pages: 600-600
  • DOI: 10.1186/2193-1801-2-600
  • Peer Reviewed
• [Journal Article] 尿路結石症の遺伝子多形 (2012)
  • Author(s): 安井 孝周、濵本 周造、岡田 淳志、郡 健二郎
  • Journal Title: 臨床検査 Volume: 56 Pages: 303-308
• [Journal Article] 尿路結石 (2012)
  • Author(s): 郡 健二郎、濵本 周造、新美 和寛
  • Journal Title: 診断と治療 Volume: 100 Pages: 292-298
• [Journal Article] Successful treatment of primary malignant lymphoma of the penis by organ-preserving rituximab-containing chemotherapy (2012)
  • Author(s): Hamamoto Shuzo, Tozawa Keiichi, Nishio Hidenori, Kawai Noriyasu
  • Journal Title: Int J Clin Oncol Volume: 17 Issue: 2 Pages: 181-184
  • DOI: 10.1007/s10147-011-0273-8
  • NAID: 10030626659
  • Peer Reviewed
• [Journal Article] Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice (2012)
  • Author(s): Hirose M, Tozawa K, Okada A, Hamamoto S, Higashibata Y, Gao B, Hayashi Y, Shimizu H, Kubota Y, Yasui T, Kohri K
  • Journal Title: Urol Res. Volume: 40 Issue: 2 Pages: 121-9
  • DOI: 10.1007/s00240-011-0400-z
  • Peer Reviewed
• [Presentation] 尿路結石の分子機構の解明と溶解療法に向けた研究戦略 (2015)
  • Author(s): 1.安井 孝周、田口 和己、濵本 周造、岡田 淳志、戸澤 啓一、郡 健二郎
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂（石川県・金沢市）
  • Year and Date: 2015-04-18 – 2015-04-22
• [Presentation] 経皮的腎砕石術におけるReal-time virtual sonography (RVS)を用いた腎瘻穿刺法の確立 (2015)
  • Author(s): 10.濵本 周造、安井 孝周、奥田 奈保子、小岩 哲、内木 拓、岡田 淳志、神谷 浩行、藤田 圭治、橋本 良博、戸澤 啓一、岩瀬 豊、郡 健二郎
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂（石川県・金沢市）
  • Year and Date: 2015-04-18 – 2015-04-22
• [Presentation] Real-time virtual sonography-guided renal access for endoscopic combined intrarenal surgery. (2015)
  • Author(s): 12.Hamamoto Shuzo, Yasui Takahiro, Okada Atsushi, Taguchi Kazumi, Okuda Naoko, Koiwa Satoshi, Kamiya Hiroyuki, Hashimoto Yoshihiro, Tozawa Keiichi, Iwase Yutaka, Kohri Kenjiro
  • Organizer: The 30th Annual Congress of the European Association of Urology
  • Place of Presentation: Madrid（Spain）
  • Year and Date: 2015-03-20 – 2015-03-24
• [Presentation] 「腹臥位」によるTULとPNLの同時治療法の開発～３D-CTによる腹臥位治療の有用性の検討～ (2013)
  • Author(s): 浜本 周造、安井 孝周、小岩 哲、伊勢呂 哲也、飯田 啓太郎、神谷 浩行、橋本 良博、藤田 圭治、林 祐太郎、岩瀬 豊、郡 健二郎
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: さっぽろ芸術文化の館（札幌）
• [Presentation] 腎結石の新規防御法の開発に向けたM-CSF誘導による抗炎症性マクロファージ(M2)の解析 (2013)
  • Author(s): 田口 和己、岡田 淳志、安井 孝周、新美 和寛、浜本 周造、戸澤 啓一、郡 健二郎
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: さっぽろ芸術文化の館（札幌）
• [Presentation] 腎結石の溶解療法の開発に向けたマクロファージによるシュウ酸カルシウム結晶の貪食機序の解明 (2013)
  • Author(s): 岡田 淳志、安井 孝周、田口 和己、藤井 泰普、浜本 周造、伊藤 恭典、戸澤 啓一、郡 健二郎
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: さっぽろ芸術文化の館（札幌）
• [Presentation] Successful results of endoscopic combined intrarenal surgery against large calculi; simultaneous use of flexible ureteroscopy and mini-percutaneous nephrolithotomy overcame the drawbacks of the monotherapy of percutaneous nephrolithotomy. (2013)
  • Author(s): Hamamoto Shuzo, Yasui Takahiro, Koiwa Satoshi, Isero Tetsuya, Okada Atsushi, Kamiya Hiroyuki, Hashimoto Yoshihiro, Fujita Keiji, Tozawa Keiichi, Iwase Yutaka, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: San Diego Convention Center( San Diego, USA)
• [Presentation] The technique of endoscopic combined intrarenal surgery in the prone splint-leg position: Prone position is suitable for simultaneous operation of flexible ureteroscopy and mini-percutaneous nephrolithotomy. (2013)
  • Author(s): Hamamoto Shuzo, Yasui Takahiro, Koiwa Satoshi, Isero Tetsuya, Kamiya Hiroyuki, Okada Atsushi, Taguchi Kazumi, Hashimoto Yoshihiro, Tozawa Keiichi, Iwase Yutaka, Kohri Kenjiro
  • Organizer: 2nd Meeting of the EAU Section of Urolithiasis
  • Place of Presentation: the Hotel Scandic Copenhagen（コペンハーゲン、デンマーク）
• [Presentation] 細径腎盂鏡にTULを併用したサンゴ状結石治療 (2013)
  • Author(s): 浜本 周造、安井 孝周、岡田 淳志、小岩 哲、伊勢呂 哲也、神谷 浩行、橋本 良博、戸澤 啓一、岩瀬 豊、郡 健二郎
  • Organizer: 第27回日本泌尿器内視鏡学会総会
  • Place of Presentation: ウェスティンナゴヤキャッスル（名古屋）
• [Presentation] 腎結石に対する治療法の工夫―小径腎盂鏡を用いたTUL併用細経PNLシステムの確立―。 (2012)
  • Author(s): 濵本 周造、安井 孝周、岡田 淳志、岩月 正一郎、田口 和己、藤井 泰普、河合 憲康、戸澤 啓一、藤田 圭治、郡 健二郎
  • Organizer: 第100回日本泌尿器科学会総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
• [Presentation] A specific antibody against thrombin-cleaved osteopontin contributes to inhibition of renal crystal formation in mice. (2012)
  • Author(s): Hamamoto S, Yasui T, Okada A, Niimi K, Taguchi K, Tozawa K, Kohri K
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: Atlanta(USA)
• [Presentation] Antigen-specific induction of thrombin-cleaved form of osteopontin contributes to inhibit renal stone formation. (2012)
  • Author(s): Hamamoto S, Yasui T, Okada A, Niimi K, Tozawa K, Kohri K
  • Organizer: 第32回国際泌尿器科学会（SIU）
  • Place of Presentation: 福岡国際会議場(福岡県)