Diurnal change of urothelial function focusing on the hemichannel of connexin43

• Project/Area Number: 25893100
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Kyoto University
• Principal Investigator: NEGORO Hiromitsu 京都大学, 医学(系)研究科(研究院), 助教 (80708595)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 体内時計 / 尿路上皮 / コネキシン43 / ヘミチャネル

Outline of Final Research Achievements

We have found that major clock genes and connexin43 (Cx43), a gap junction protein in the bladder, were expressed in the circadian manner in two immortalized human urothelial cells (TRT-HU1 and nhu-hTERT) by synchronizing the clock in each cells using serum shock method. To address whether Cx43 has a function as hemichannel, overexpression/knock down of Cx43 were induced in these cells. The amount of ATP release from nhu-TERT with Cx43 overexpression was higher compared with that from the control. On the other hand, the amount of ATP release by mechanical stimulation was smaller in TRT-HU1 with knock down of Cx43 or with addition of hemichannel inhibitors than that in their controls. These results indicate that one of the pathways of ATP release is the Cx43 hemichannel in these urothelial cells.
We presently progress the research to investigate whether the amount of ATP release has diurnal change and how the role of urethral Cx43 for the bladder function by using mouse model.

Research Products

• [Journal Article] Pannexin 1 channels play essential roles in urothelial mechanotransduction and intercellular signaling. (2014)
  • Author(s): Negoro H, Urban-Maldonado M, Liou LS, Spray DC, Thi MM, Suadicani SO.
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: e106269-e106269
  • DOI: 10.1371/journal.pone.0106269
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Altered detrusor gap junction communications induce storage symptoms in bladder inflammation: a mouse cyclophosphamide-induced model of cystitis. (2014)
  • Author(s): Okinami T, Imamura M, Nishikawa N, Negoro H, Sugino Y, Yoshimura K, Kanematsu A, Hashitani H, Ogawa O.
  • Journal Title: PLoS One Volume: 9 Issue: 8 Pages: e104216-e104216
  • DOI: 10.1371/journal.pone.0104216
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Pannexin 1 channels participate in urothelial ATP release and signaling (2014)
  • Author(s): 根来宏光
  • Organizer: International Continence Society 2014
  • Place of Presentation: Rio de Janeiro, Brasil
  • Year and Date: 2014-10-20 – 2014-10-24
• [Presentation] Coordination of day-night changes in urination by the circadian clock (2014)
  • Author(s): 根来宏光
  • Organizer: 筑波グローバルサイエンス シンポジウム
  • Place of Presentation: 筑波大学
  • Year and Date: 2014-09-28
  • Invited
• [Presentation] 未来につながる排尿基礎研究 (2014)
  • Author(s): 根来宏光
  • Organizer: 第21回排尿機能学会 シンポジウム
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2014-09-17 – 2014-09-20
  • Invited
• [Presentation] 尿路上皮とコネキシンの時間生物学 (2014)
  • Author(s): 根来宏光
  • Organizer: 第102回日本泌尿器科学会総会 ヤングリサーチグラント報告
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2014-04-23 – 2014-04-27
• [Presentation] 排尿を司る体内時計 (2014)
  • Author(s): 根来宏光
  • Organizer: 第102回日本泌尿器科学会総会 教育講演
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2014-04-23 – 2014-04-27
  • Invited