Investigation of the effect of anti-osteopontin antibody on renal crystal formation

• Project/Area Number: 25462518
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: Homma hideki 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (20260789)
• Co-Investigator(Kenkyū-buntansha): Kohri Kenjiro 名古屋市立大学, 学長 (30122047) ; Tozawa Keiichi 名古屋市立大学, 大学院医学研究科, 准教授 (40264733) ; Yasui takahiro 名古屋市立大学, 大学院医学研究科, 教授 (40326153) ; Okada Atsushi 名古屋市立大学, 大学院医学研究科, 講師 (70444966) ; HAMAMOTO Shuzo 名古屋市立大学, 大学院医学研究科, 助教 (80551267)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腎結石 / オステオポンチン / 尿路結石 / サル

Outline of Final Research Achievements

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 on renal crystal formation. Scanning electron microscopy showed that the crystals in 35B6-Ab-treated mice were aberrantly formed and their density was low. Microstructure analysis of renal tubular cells by transmission electron microscopy revealed that untreated mice showed collapsed mitochondria in the flattened cytoplasm of renal tubular cells. In vitro, 35B6-Ab was found to inhibit the attachment of 14C-labeled crystals to renal tubular culture cells and reduce morphological damage of these cells.
In conclusion, 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] Proinflammatory and Metabolic Changes Facilitate Renal Crystal Deposition in an Obese Mouse Model of Metabolic Syndrome. (2015)
  • Author(s): Taguchi K, Okada A, Hamamoto S, Iwatsuki S, Naiki T, Ando R, Mizuno K, Tozawa K, Kohri K, Yasui T.
  • Journal Title: J Urol. Volume: 194 Issue: 6 Pages: 1787-96
  • DOI: 10.1016/j.juro.2015.07.083
  • Peer Reviewed / Open Access
• [Journal Article] First case report of staghorn calculi successfully removed by mini-endoscopic combined intrarenal surgery in a 2-year-old boy. (2015)
  • Author(s): Taguchi Kazumi, Hamamoto Shuzo, Okada Atsushi, Mizuno Kentaro, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro, Yasui Takahiro
  • Journal Title: International Journal of Urology Volume: 22 Issue: 10 Pages: 978-80
  • DOI: 10.1111/iju.12860
  • Peer Reviewed
• [Journal Article] Laparoscopic versus open radical cystectomy for patients older than 75 years: a single-center comparative analysis. (2015)
  • Author(s): Yasui Takahiro, Tozawa Keiichi, Ando Ryosuke, Hamakawa Takashi, Iwatsuki Shoichiro, Taguchi Kazumi, Kobayashi Daichi, Naiki Taku, Mizuno Kentaro, Okada Atsushi, Umemoto Yukihiro, Kawai Noriyasu, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Journal Title: Asian Pacific Journal of Cancer Prevention Volume: 16 Issue: 15 Pages: 6353-6358
  • DOI: 10.7314/apjcp.2015.16.15.6353
  • Peer Reviewed
• [Journal Article] The association between the incidence of urolithiasis and nutrition based on Japanese National Health and Nutrition Surveys (2013)
  • Author(s): Yasui T, Okada A, Hamamoto S, Hirose M, Ando R, Kubota Y, Tozawa K, Hayashi Y, Gao B, Suzuki S, Kohri K
  • Journal Title: Urolithiasis Volume: 41 Issue: 3 Pages: 217-24
  • DOI: 10.1007/s00240-013-0567-6
  • Peer Reviewed
• [Journal Article] Impact of official technical training for urologists on the efficacy of shock wave lithotripsy. (2013)
  • Author(s): Okada A, Yasui T, Taguchi K, Niimi K, Hirose Y, Hamamoto S, Ando R, Kubota Y, Umemoto Y, Tozawa K, Sasaki S, Hayashi Y, Kohri K.
  • Journal Title: Urolithiasis. Volume: 41 Issue: 6 Pages: 287-492
  • DOI: 10.1007/s00240-013-0586-3
  • 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): kada 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): 74. 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
• [Presentation] Image guided percutaneous access: What is the best approach? Fluoro guided Vs. Ultrasound guided. (2015)
  • Author(s): Hamamoto Shuzo, Yasui Takahiro
  • Organizer: EASE 2015
  • Place of Presentation: Manila（Republic of the Philippines）
  • Year and Date: 2015-11-26
  • Int'l Joint Research / Invited
• [Presentation] 尿路結石分子標的治療を目指した網羅的遺伝子解析によるRandall’s Plaqueの発症制御遺伝子の同定。 (2015)
  • Author(s): 田口 和己、浜本 周造、海野 怜、宇佐美 雅之、伊藤 靖彦、広瀬 真仁、安藤 亮介、岡田 淳志、藤田 圭治、戸澤 啓一、安井 孝周、郡 健二郎
  • Organizer: 日本尿路結石症学会第25回学術集会
  • Place of Presentation: ロワジールホテル旭川（北海道旭川市）
  • Year and Date: 2015-08-28
• [Presentation] eterminants of health-related quality of life for patients after urinary lithotripsy: ureteroscopic versus shock wave lithotripsy. (2015)
  • Author(s): Hamamoto Shuzo, Yasui Takahiro, Okuda Naoko, Koiwa Satoshi, Okada Atsushi, Kamiya Hiroyuki, Hashimoto Yoshihiro, Tozawa Keiichi, Iwase Yutaka, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2015
  • Place of Presentation: New Orleans（USA）
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] Genetic diagnosis trial by single nucleotide polymorphism analysis from a case-control study, using three novel loci associated with susceptibility to urolithiasis from a genome-wide association study (GWAS) (2015)
  • Author(s): Yasui Takahiro, Okada Atsushi, Usami Masayuki, Hamamoto Shuzo, Ando Ryosuke, Itoh Yasunori, Tozawa Keiichi, Sasaki Shoichi, Hayashi Yutaro, Sato Yoshikazu, Higashi Yoshihito, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2015
  • Place of Presentation: New Orleans（USA）
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [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): 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、ANAクラウンプラザホテル金沢 他（石川県金沢市）
  • Year and Date: 2015-04-18
  • Invited
• [Presentation] 尿路結石の破砕効果を高める正しい修得法。 (2015)
  • Author(s): 岡田 淳志、田口 和己、安藤 亮介、安井 孝周、梅本 幸裕、河合 憲康、戸澤 啓一、佐々木 昌一、林 祐太郎、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、ANAクラウンプラザホテル金沢 他（石川県金沢市）
  • Year and Date: 2015-04-18
• [Presentation] シュウ酸カルシウム結石の発生母地「Randall’s Plaque」の制御因子同定による尿路結石分子標的治療の開発 (2015)
  • Author(s): 田口 和己、海野 怜、濵本 周造、安藤 亮介、金本 一洋、岡田 淳志、安井 孝周、藤田 圭治、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、ANAクラウンプラザホテル金沢 他（石川県金沢市）
  • Year and Date: 2015-04-18
• [Presentation] 尿路結石の成因からみた予防法。 (2013)
  • Author(s): 郡 健二郎、岡田 淳志
  • 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] 薬物療法の未来と再発予防 (2013)
  • Author(s): 安井 孝周
  • Organizer: 第101回日本泌尿器科学会総
  • Place of Presentation: さっぽろ芸術文化の館（札幌）
• [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): 濵本 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] ゲノムワイド関連解析による尿路結石の新規遺伝子領域の同定と発症リスク診断法への応用 (2013)
  • Author(s): 25. 安井 孝周、岡田 淳志、宇佐美 雅之、伊藤 恭典、戸澤 啓一、東 義人、佐藤 嘉一、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): 28. 岡田 淳志、安井 孝周、田口 和己、藤井 泰普、濵本 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; (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] Effect of an ultrasonic targeting method for kidney and proximal ureter stones on the success rate of shock wave lithotripsy. (2013)
  • Author(s): Okada Atsushi, Taguchi Kazumi, Ando Ryosuke, Umemoto Yukihiro, Itoh Yasunori, Yasui Takahiro, Sasaki Shoichi, Kohri Kenjiro, Hamamoto Shuzo:
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: San Diego Convention Center( San Diego, USA)
• [Presentation] 尿路結石のゲノムワイド解析による再発リスク診断法の確立 (2013)
  • Author(s): 安井 孝周、岡田 淳志、新美 和寛、田口 和己、戸澤 啓一、郡 健二郎
  • Organizer: 第56回 日本腎臓学会学術総会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] Association of the loci 5q35.3, 7p14.3 and 13q14.1 with urolithiasis in the Japanesse population. (2013)
  • Author(s): Yasui Takahiro, Okada Atsushi, Usami Masayuki, Ito Yasuhiko, Taguchi Kazumi, Fujii Yasuhiro, Niimi Kazuhiro, Hamamoto Shuzo, Ando Ryosuke, Hirose Masahito, Itoh Yasunori, Tozawa Keiichi, Higashi Yoshikazu, Sato Yoshikazu, Matsuda Koichi, 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] The technique of endoscopic combined intrarenal surgery in the prone splint-leg position: (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）
• [Book] Annual Review 腎臓 2013 (2013)
  • Author(s): 岡田 淳志、郡 健二郎
  • Publisher: 中外医学社