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タイトル: Circadian coordination of ATP release in the urothelium via connexin43 hemichannels
著者: Sengiku, Atsushi
Ueda, Masakatsu
Kono, Jin
Sano, Takeshi
Nishikawa, Nobuyuki
Kunisue, Sumihiro
Tsujihana, Kojiro
Liou, Louis S.
Kanematsu, Akihiro
Shimba, Shigeki
Doi, Masao  kyouindb  KAKEN_id
Okamura, Hitoshi
Ogawa, Osamu
Negoro, Hiromitsu
著者名の別形: 上田, 政克
河野, 仁
國末, 純宏
土居, 雅夫
岡村, 均
小川, 修
根来, 宏光
発行日: 31-Jan-2018
出版者: Springer Nature
誌名: Scientific reports
巻: 8
論文番号: 1996
抄録: Day-night changes in the storage capacity of the urinary bladder are indispensable for sound sleep. Connexin 43 (Cx43), a major gap junction protein, forms hemichannels as a pathway of ATP in other cell types, and the urinary bladder utilizes ATP as a mechanotransduction signals to modulate its capacity. Here, we demonstrate that the circadian clock of the urothelium regulates diurnal ATP release through Cx43 hemichannels. Cx43 was expressed in human and mouse urothelium, and clock genes oscillated in the mouse urothelium accompanied by daily cycles in the expression of Cx43 and extracellular ATP release into the bladder lumen. Equivalent chronological changes in Cx43 and ATP were observed in immortalized human urothelial cells, but these diurnal changes were lost in both arrhythmic Bmal1-knockout mice and in BMAL1-knockdown urothelial cells. ATP release was increased by Cx43 overexpression and was decreased in Cx43 knockdown or in the presence of a selective Cx43 hemichannel blocker, which indicated that Cx43 hemichannels are considered part of the components regulating ATP release in the urothelium. Thus, a functional circadian rhythm exists in the urothelium, and coordinates Cx43 expression and function as hemichannels that provide a direct pathway of ATP release for mechanotransduction and signalling in the urothelium.
著作権等: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: http://hdl.handle.net/2433/234202
DOI(出版社版): 10.1038/s41598-018-20379-0
PubMed ID: 29386573
出現コレクション:学術雑誌掲載論文等

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