Biomolecular mechanism of urinary stone formation, and development of medicine

• Project/Area Number: 24659716
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: KENJIRO Kohri 名古屋市立大学, その他部局等, 学長 (30122047)
• Co-Investigator(Kenkyū-buntansha): 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): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 尿路結石 / オステオポンチン / ミトコンドリア / マクロファージ

Outline of Final Research Achievements

(1) 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. (2) To experimentally evaluate the clinical application of N-methyl-4-isoleucine cyclosporin, a novel selective inhibitor of cyclophilin D activation.We first report a new treatment agent determining renal calcium crystallization through cyclophilin D activation. (3)M2Mφ transfusion directly suppressed crystal formation and the marked crystal phagocytic ability of M2Mφs.

Research Products

• [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] Novel effect of the inhibitor of mitochondrial cyclophilin D activation, N-methyl-4-isoleucine cyclosporin, on renal calcium crystallization (2014)
  • Author(s): Niimi K, Yasui T, Okada A, Hirose Y, Kubota Y, Umemoto Y, Kawai N, Tozawa K, Kohri K
  • Journal Title: Int J Urol Volume: ― Issue: 7 Pages: 707-13
  • DOI: 10.1111/iju.12425
  • Peer Reviewed
• [Journal Article] A Paracrine Mechanism Involving Renal Tubular Cells, Adipocytes, and Macrophages Promotes Kidney Stone Formation in a Simulated Metabolic Syndrome Environment. (2014)
  • Author(s): Li Zuo, Okada Atsushi, Yasui Takahiro, Taguchi Kazumi, Ito Yasuhiko, Hirose Yasuhiko, Fujii Yasuhiro, Niimi Kazuhiro, Hamamoto Shuzo, Ando Ryosuke, Itoh Yasunori, Zuo Jiangang, Tozawa Keiichi, Kohri Kenjiro
  • Journal Title: The Journal of Urology Volume: 191 Issue: 6 Pages: 1906-1912
  • DOI: 10.1016/j.juro.2014.01.013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Long-term follow-up of nephrotoxicity in rats administered both melamine and cyanuric acid. (2014)
  • Author(s): Yasui T, Kobayashi T, Okada A, Hamamoto S, Hirose M, Mizuno K, Kubota Y, Umemoto Y, Kawai N, Tozawa K, Gao B, Kohri K.
  • Journal Title: BMC Res Notes. Volume: 7 Issue: 1 Pages: 87-87
  • DOI: 10.1186/1756-0500-7-87
  • Peer Reviewed / Open Access
• [Journal Article] Colony-stimulating factor-1 signaling suppresses renal crystal formation. (2014)
  • Author(s): Taguchi K, Okada A, Kitamura H, Yasui T, Naiki T, Hamamoto S, Ando R, Mizuno K, Kawai N, Tozawa K, Asano K, Tanaka M, Miyoshi I, Kohri K.
  • Journal Title: J Am Soc Nephrol. Volume: －
  • Peer Reviewed
• [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] Effect of Adiponectin on Kidney Crystal Formation in Metabolic Syndrome Model Mice via Inhibition of Inflammation and Apoptosis (2013)
  • Author(s): Fujii Y, Okada A, Yasui T, Niimi K,Hamamoto S, Hirose M, Kubota Y, Tozawa K, Hayashi Y, Kohri K.
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e61343-e61343
  • DOI: 10.1371/journal.pone.0061343
  • Peer Reviewed
• [Journal Article] Kidney stone formation is positively associated with conventional risk factors for coronary heart disease in Japanese men. (2013)
  • Author(s): Ando R, Nagaya T, Suzuki S, Takahashi H, Kawai M, Okada A, Yasui T, Kubota Y, Umemoto Y, Tozawa K, Kohri K.
  • Journal Title: Journal of urology Volume: 189 Issue: 4 Pages: 1340-1346
  • DOI: 10.1016/j.juro.2012.11.045
  • Peer Reviewed
• [Journal Article] Biomolecular mechanism of urinary stone formation involving osteopontin (2012)
  • Author(s): Kohri K
  • Journal Title: Urol Res Volume: 40 Issue: 6 Pages: 623-637
  • DOI: 10.1007/s00240-012-0514-y
  • Peer Reviewed
• [Journal Article] Pioglitazone, a peroxisome proliferator activated receptor γ agonist, decreases renal crystal deposition, oxidative stress and inflammation in hyperoxaluric rats (2012)
  • Author(s): Taguchi K
  • Journal Title: J Urol Volume: 188 Issue: 3 Pages: 1002-1011
  • DOI: 10.1016/j.juro.2012.04.103
  • Peer Reviewed
• [Journal Article] Mitocondrial permeability transition pore opening induces the initial process of renal calcium crystallization (2012)
  • Author(s): Niimi Kazuhiro, Yasui Takahiro, Hirose Masahito, Hamamoto Shuzo, Itoh Yasunori, Okada Atsushi, Kubota Yasue, Kojima Yoshiyuki, Tozawa Keiichi, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Journal Title: Free Radical Biology & Medicine Volume: 52 Issue: 7 Pages: 1207-1217
  • DOI: 10.1016/j.freeradbiomed.2012.01.005
  • Peer Reviewed
• [Presentation] 尿路結石の分子機構の解明と溶解療法に向けた治療戦略 (2015)
  • Author(s): 安井孝周、田口和己、濵本周造、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 – 2015-04-21
  • Invited
• [Presentation] ミトコンドリアcyclophilin Dをターゲットとした尿路結石に対する新規治療薬と尿中バイオマーカーの開発 (2014)
  • Author(s): 新美和寛、藤井泰普、伊藤靖彦、高田英輝、広瀬真仁、岡田淳志、窪田泰江、安井孝周、戸澤啓一、郡健二郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] マルチプレックス解析を用いた尿路結石患者に特異的な尿中マクロファージ関連因子の同定 (2014)
  • Author(s): 岡田淳志、田口和己、藤井泰普、新美和寛、濵本周造、安井孝周、広瀬真仁、戸澤啓一、郡健二郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [Presentation] 腎結石溶解療法の開発を目指した抗炎症マクロファージ（M2）による結晶貪食作用の解明 (2014)
  • Author(s): 田口和己、岡田淳志、安井孝周、廣瀬泰彦、新美和寛、濵本周造、安藤亮介、伊藤恭典、戸澤啓一、郡健二郎
  • Organizer: 第102回日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27
• [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（札幌市）
• [Presentation] ミトコンドリアcyclophilin Dをターゲットとした尿路結石に対する治療薬の開発とバイオマーカーの確立 (2013)
  • Author(s): 新美和寛、安井孝周、広瀬真仁、岡田淳志、伊藤靖彦、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（札幌市）
• [Presentation] 薬物療法の未来と再発予防 (2013)
  • Author(s): 安井孝周、新美和寛、浜本周造、岡田淳志、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（札幌市）
  • Invited
• [Presentation] Management of stone disease in the 21st century (2013)
  • Author(s): Takahiro Yasui
  • Organizer: 2013 (108th) Annual Meeting of American Urological Association
  • Place of Presentation: San Diego Convention Center (San Diego, アメリカ合衆国)
  • Invited
• [Presentation] Anti-inflammatory M2 macrophages suppress renal crystal formation via a colony stimulating factor-1 dependent pathway in M2-deficient (op/op) mice (2013)
  • Author(s): Kazumi Taguchi, Atsushi Okada, Takahiro Yasui, Kazuhiro Niimi, Yasuhiro Fujii, Shuzo Hamamoto, Masahito Hirose, Yukihiro Umemoto, Shoichi Sasaki, Kenjiro Kohri
  • Organizer: 2013 (108th) Annual Meeting of American Urological Association
  • Place of Presentation: San Diego Convention Center (San Diego, アメリカ合衆国)