Development of crystal dissolve therapy by analyzing two macrophage phenotypes

• Project/Area Number: 25861443
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: Taguchi Kazumi 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (00595184)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腎結石 / マクロファージ / 炎症 / Randall's plaque / マイクロアレイ / マルチプレックス解析 / macrophage / 結晶貪食 / 結晶付着 / Randall's Plaque / シュウ酸カルシウム結石 / M-CSF / M1 / M2

Outline of Final Research Achievements

In vivo study using stone model mice showed that renal crystal formation increased by M1Mφ treatment whereas decreased by M2Mφ treatment.
Urinary protein multiplex analysis demonstrated that the expression of IL-4, G-CSF, and IL-1a, which were associated with M2Mφ and neutrophil, was decreased in stone-patients.
Gene expression profile of renal papillary tissue by microarray analysis revealed that stone-patients had higher expression of M1Mφ-related genes but lower expression of M2Mφ-related genes.

Research Products

• [Journal Article] Differential Roles of Peroxisome Proliferator-Activated Receptor-α and Receptor-γ on Renal Crystal Formation in Hyperoxaluric Rodents (2016)
  • Author(s): Taguchi K, Okada A, Hamamoto S, Unno R, Kobayashi T, Ando R, Tozawa K, Gao B, Kohri K, Yasui T
  • Journal Title: PPAR Res Volume: 2016 Pages: 9605890-9605890
  • DOI: 10.1155/2016/9605890
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] 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] Endoscopic combined intrarenal surgery for large calculi: Simultaneous use of flexible ureteroscopy and mini-percutaneous nephrolithotomy overcomes the disadvantageous of percutaneous nephrolithotomy monotherapy. (2014)
  • Author(s): Hamamoto Shuzo, Yasui Takahiro, Okada Atsushi, Taguchi Kazumi, Kawai Noriyasu, Ando Ryosuke, Mizuno Kentaro, Kubota Yasue, Kamiya Hiroyuki, Tozawa Keiichi, Kohri Kenjiro
  • Journal Title: Journal of Endourology Volume: 28 Issue: 1 Pages: 28-33
  • DOI: 10.1089/end.2013.0361
  • 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] 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] 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, MizunoK, Kawai N, Tozawa K, Asano K, Tanaka M, Miyoshi I, Kohri K
  • Journal Title: Journal of the American Society of Nephrology Volume: ―
  • Peer Reviewed
• [Presentation] The role of M1/M2 macrophages for CaOx stone and Randall’s plaque formation. (2016)
  • Author(s): Taguchi Kazumi, Okada Atsushi, Hamamoto Shuzo, Unno Rei, Kamisawa Hideyuki, Naiki Taku, Ando Ryosuke, Umemoto Yukihiro, Itoh Yasunori, Tozawa Keiichi, Kohri Kenjiro, Yasui Takahiro
  • Organizer: The 31th Annual Congress of the European Association of Urology
  • Place of Presentation: Munich (German)
  • Year and Date: 2016-03-11
  • Int'l Joint Research
• [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] Hypercalciuria and migration of inflammatory macrophages play key roles for kidney stone formation in metabolic syndrome. (2015)
  • Author(s): Taguchi Kazumi, Unno Rei, Fujii Yasuhiro, Hamamoto Shuzo, Ando Ryosuke, Okada Atsushi, Yasui Takahiro, Fujita Keiji, Tozawa Keiichi, Hayashi Yutaro, 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] Gene expression profile of Randall’s plaque in idiopathic CaOx stone formers suggests dysregulation of Mφ-related genes. (2015)
  • Author(s): Taguchi Kazumi, Unno Rei, Fujii Yasuhiro, Naiki Taku, Hamamoto Shuzo, Ando Ryosuke, Kanemoto Kazuhiro, Okada Atsushi, Yasui Takahiro, Tozawa Keiichi, Hayashi Yutaro, 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] PPAR-α/γ agonists have different effects on renal crystal formation in hyperoxaluric animal models. (2015)
  • Author(s): Taguchi Kazumi, Unno Rei, Hirose Yasuhiko, Hamamoto Shuzo, Kobayashi Takahiro, Ando Ryosuke, Okada Atsushi, Itoh Yasunori, Yasui, Takahiro, Tozawa Keiichi, Hayashi Yutaro, 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] M2 macrophages eliminate renal crystals by phagocytosis. (2014)
  • Author(s): Taguchi Kazumi, Okada Atsushi, Yasui Takahiro, Unno Rei, Niimi Kazuhiro, Tozawa Keiichi, Sasaki Shoichi, Hayashi Yutaro, Kohri Kenjiro
  • Organizer: 2nd of Experts in Stone Disease
  • Place of Presentation: ケープタウン（南アフリカ）
  • Year and Date: 2014-12-10 – 2014-12-13
• [Presentation] 腎結石溶解療法の開発を目指した抗炎症性マクロファージ（M2）による結晶貪食作用の解明。 (2014)
  • Author(s): 田口 和己
  • Organizer: 第65回名古屋市立大学医学会総会
  • Place of Presentation: 名古屋市立大学（愛知県名古屋市）
  • Year and Date: 2014-12-07
  • Invited
• [Presentation] 腎結石防御に向けた抗炎症型マクロファージの機能解明と治療薬への応用。 (2014)
  • Author(s): 田口 和己、安井 孝周、岡田 淳志、新美 和寛
  • Organizer: 平成25年度愛知腎臓財団助成研究発表会
  • Place of Presentation: ウィルあいち（愛知県名古屋市）
  • Year and Date: 2014-06-07
• [Presentation] 腎結石溶解療法の開発を目指した抗炎症性マクロファージ(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] PPAR-α/γ agonist have different effects on renal crystal formation in hyperoxaluric animal models (2014)
  • Author(s): Taguchi Kazumi, Okada Atsushi, Yasui Takahiro, Iwatsuki Shoichiro, Hamakawa Takashi, Hirose Yasuhiko, Kobayashi Takahiro, Hamamoto Shuzo, Ando Ryosuke, Itoh Yasunori, Tozawa Keiichi, Kohri Kenjiro
  • Organizer: 29th Annual EAU Congress
  • Place of Presentation: ストックホルム（スウェーデン）
  • Year and Date: 2014-04-11 – 2014-04-15
• [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
  • 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
  • Place of Presentation: さっぽろ芸術文化の館（札幌）
• [Presentation] CSF-1誘導による抗炎症マクロファージ（M2）を用いた腎結石の新規防御法の開発 (2013)
  • Author(s): 田口 和己、岡田 淳志、安井 孝周、新美 和寛、安藤 亮介、戸澤 啓一、郡 健二郎
  • Organizer: 第56回日本腎臓学会
  • Place of Presentation: 東京国際フォーラム（東京）
• [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): Taguchi Kazumi, Okada Atsushi, Yasui Takahiro, Niimi Kazuhiro, Fujii Yasuhiro, Hamamoto Shuzo, Hirose Masahito, Umemoto Yukihiro, Sasaki Shoichi, Kohri Kenjiro
  • Organizer: American Urological Association Annual Meeting 2013
  • Place of Presentation: San Diego Convention Center( San Diego, USA)
• [Presentation] M2 macrophages phagocytose renal calcium oxalate crystals and suppress crystal formation in a colony-stimulating factor-1-dependent manner. (2013)
  • Author(s): Taguchi Kazumi, Okada Atsushi, Yasui Takahiro, Hirose Yasuhiko, Niimi Kazuhiro, Hamamoto Shuzo, Itoh Yasunori, Tozawa Keiichi, 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] 腎結石溶解療法に向けたマクロファージ機能解析 (2013)
  • Author(s): 岡田 淳志、安井 孝周、田口 和己、藤井 泰普、新美 和寛、浜本 周造、広瀬 真仁、戸澤 啓一、郡 健二郎
  • Organizer: 第63回日本泌尿器科学会中部総会
  • Place of Presentation: 愛知県産業労働センター（名古屋）
  • Invited
• [Book] 病気とくすり 基礎と実践 Expert’s Guide 泌尿器系・生殖器系疾患 尿路結石 (2016)
  • Author(s): 田口 和己、安井 孝周
  • Publisher: 南山堂
• [Book] 臨床泌尿器科 4．尿路結石症 尿路結石 (2015)
  • Author(s): 田口 和己、戸澤 啓一、安井 孝周
  • Publisher: 医学書院
• [Book] 特集 尿路結石症診療ガイドライン改訂のポイント－ここが変わった－ 尿路結石症の疫学 (2015)
  • Author(s): 安井孝周、岡田淳志、安藤亮介、田口和己、戸澤啓一
  • Publisher: 医学図書出版
• [Book] メタボリックシンドロームと尿路結石，その対策。Annual Review 腎臓 2013 (2013)
  • Author(s): 岡田 淳志、郡 健二郎
  • Total Pages: 7
  • Publisher: 中外医学社