マクロファージの２つの極性に着目した結石貪食能の解析と溶解療法の開発

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25861443
• Research Institution: Nagoya City University
• Principal Investigator: 田口 和己 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
• Keywords: Randall's plaque / macrophage / 結晶貪食 / 結晶付着

Outline of Annual Research Achievements

1.骨髄由来MφからM1・M2を分化誘導し、尿細管上皮細胞との共培養を行った。各Mφによる結晶の貪食率、尿細管上皮細胞への結晶付着率をそれぞれフローサイトメトリー、共焦点顕微鏡にて評価した。その結果、M1に比べM2の結晶貪食能は高く、M2との共培養により尿細管上皮細胞の結晶付着率は低下した。
2.シュウ酸カルシウム結石患者の腎乳頭部の組織を採取し、結石の原基となるプラーク(Randall Plaque＝RP)における遺伝子発現を検討した。マイクロアレイにおいて、RP部では正常粘膜部と比べて、好中球・Mφ関連遺伝子の発現増加が認められた。定量PCRにおいて、RP部位ではM1関連遺伝子であるNOS2,CSF2,IL10,CCR2,SPP1が高値で、M2関連遺伝子であるFN1,PPARG,MRC1,CD163が低値であった。

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
  • Journal Title: PPAR Research Volume: 2016 Pages: 9605890
  • DOI: 10.1155/2016/9605890.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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: The Journal of Urology Volume: 194 Pages: 1787-1796
  • DOI: 10.1016/j.juro.2015.07.083.
  • Peer Reviewed / Acknowledgement Compliant
• [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 K, Hamamoto S, Okada A, Mizuno K, Tozawa K, Hayashi Y, Kohri K, Yasui T
  • Journal Title: International Journal of Urology Volume: 22 Pages: 978-980
  • DOI: 10.1111/iju.12860.
  • Peer Reviewed / Acknowledgement Compliant
• [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 – 2016-03-15
  • 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 – 2015-08-29
• [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 – 2015-05-19
  • 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 – 2015-05-19
  • 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 – 2015-05-19
  • Int'l Joint Research
• [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
  • Total Pages: 5(601-605)
  • 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
  • Total Pages: 4(163-166)
  • 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
  • Total Pages: 7(899-905)
  • Publisher: 医学図書出版