Novel strategy targeting mechanosensor in the bladder urothelium for treatment of unaderactive bladder

• Project/Area Number: 18K09188
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: University of Yamanashi
• Principal Investigator: KIRA Satoru 山梨大学, 大学院総合研究部, 助教 (10530115)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 泌尿器科 / 低活動膀胱 / 伸展受容器 / 泌尿器 / 泌尿器科学 / 膀胱上皮

Outline of Final Research Achievements

Based on bladder contractility index and Bladder Outlet Obstruction Index in urodynamic study, Detrusor Underactivity (DU) and Control group were defined. We collected the urothelial cells in the urine samples of all patients and analyzed the mRNA expression of each subtypes of mechanosensory molecule using quantitive real-time reverse transcription polymerase chain reaction. The mRNA expression of TRPM2 and Piezo 1 were lower level in DU group than in Contorl group. These molecules may be involved with the pathogenesis of DU.

Academic Significance and Societal Importance of the Research Achievements

低活動膀胱は、その病態生理もさることながら現時点では確立された定義や診断基準すら定まっていないのが現状である。また、本疾患の原因の一つとして、尿意知覚異常を代表とする尿意求心路異常が注目を集めているが、詳細までは解明されていない。本研究の成果からは、低活動膀胱における尿意求心路異常として膀胱尿路上皮伸展受容器の発現異常が示唆されている。本研究の成果が低活動膀胱の改善に導く可能性を示し、新規治療薬の端緒となりうると考えられた。

Research Products

• [Journal Article] Urinary metabolites identified using metabolomic analysis as potential biomarkers of nocturia in elderly men. (2020)
  • Author(s): Kira S, Mitsui T, Miyamoto T, Ihara T, Nakagomi H, Hashimoto Y, Takamatsu H, Tanahashi M, Takeda M, Tsuchiya S, Sawada N, Takeda M
  • Journal Title: World J Urol Volume: - Issue: 10 Pages: 2563-2569
  • DOI: 10.1007/s00345-019-03042-9
  • Peer Reviewed
• [Journal Article] Feasibility and necessity of the fourth arm of the da Vinci Sisurgical system for robot-assisted partial nephrectomy (2020)
  • Author(s): Satoru Kira, Takahiko Mitsui, Norifumi Sawada, Hiroshi Nakagomi, Tatsuya Ihara, Nobuhiro Takahashi, Masayuki Takeda
  • Journal Title: The international Journal of Medical Robotics and Computer Assisted Surgery. Volume: 16 Issue: 3
  • DOI: 10.1002/rcs.2092
  • Peer Reviewed
• [Journal Article] Liquid chromatography?mass spectrometry identification of serum biomarkers for nocturia in aged men (2019)
  • Author(s): Kira Satoru、Mitsui Takahiko、Miyamoto Tatsuya、Ihara Tatsuya、Nakagomi Hiroshi、Hashimoto Yuka、Takamatsu Hajime、Tanahashi Masayuki、Takeda Masahiro、Sawada Norifumi、Andersson Karl-Erik、Takeda Masayuki
  • Journal Title: World Journal of Urology Volume: in press Issue: 10 Pages: 2199-2205
  • DOI: 10.1007/s00345-019-02647-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Metabolomics Analysis of Blood Identifies Potential Biomarkers and Possible Treatment Targets for Nocturia (2019)
  • Author(s): Satoru Kira, Takahiko Mitsui, Tatsuya Miyamoto, Tatsuya Ihara, Hiroshi Nakagomi, Yuka Hashimoto, Hajime Takamatsu, Masayuki Tanahashi, Masahiro Takeda, Norifumi Sawada, Masayuki Takeda
  • Journal Title: Therapeutic Advances in Urology Volume: 11 Pages: 1-7
  • DOI: 10.1177/1756287219850087
  • Peer Reviewed / Open Access
• [Presentation] メタボロミクス解析を用いた尿意切迫感に関連する新規標的分子の網羅的探索 (2020)
  • Author(s): 吉良聡、三井貴彦、宮本達也、中込宙史、井原達矢、橋本由佳、澤田智史、武田正之
  • Organizer: 第27回日本排尿機能学会
• [Presentation] 前立腺肥大症に対するTUEB術後2年間の尿流動体検査を含めた臨床的検討 (2020)
  • Author(s): 澤田友史、井原達也、佐藤毅、古屋良太、矢野文彬、望月孝規、吉良聡、中込宙史、三井貴彦、武田正之
  • Organizer: 第27回日本排尿機能学会
• [Presentation] 新規診断ツールとしての尿中上皮細胞の可能性 (2019)
  • Author(s): 吉良 聡、三井 貴彦、澤田 智史、中込 宙史、井原 達矢、土屋 幸子、 武田 正之
  • Organizer: 第26回日本排尿機能学会
• [Presentation] 侵襲的UDSのサローゲートマーカーとしての尿中細胞の可能性 (2019)
  • Author(s): 吉良 聡
  • Organizer: 第107回日本泌尿器科学会総会