2012年12月
ASK3 responds to osmotic stress and regulates blood pressure by suppressing WNK1-SPAK/OSR1 signaling in the kidney
NATURE COMMUNICATIONS
- 巻
- 3
- 号
- 開始ページ
- 1285
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/ncomms2283
- 出版者・発行元
- NATURE PUBLISHING GROUP
Changes in the osmolality of body fluids pose a serious danger to cells and living organisms, which have developed cellular systems to sense and respond to osmotic stress and to maintain homoeostasis of body fluid. However, these processes are incompletely understood in mammals. Here we show that apoptosis signal-regulating kinase 3 (ASK3) is predominantly expressed in the kidney and alters its kinase activity bidirectionally in response to osmotic stress. We further demonstrate that ASK3 interacts with WNK1, mutation in which causes an inherited form of hypertension in humans. Knockdown of Ask3 by short interfering RNA enhances the activation of the WNK1-SPAK/OSR1 signalling pathway. Moreover, Ask3 knockout mice exhibit a hypertensive phenotype, in addition to hyperactivation of SPAK/OSR1 in renal tubules. Our results suggest that ASK3 is a unique bidirectional responder to osmotic stress and that it has a role in the control of blood pressure as an upstream suppressor of the WNK1-SPAK/OSR1 signalling pathway.
- リンク情報
-
- DOI
- https://doi.org/10.1038/ncomms2283
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201502809496268906
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/23250415
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000316356700052&DestApp=WOS_CPL
- ID情報
-
- DOI : 10.1038/ncomms2283
- ISSN : 2041-1723
- J-Global ID : 201502809496268906
- PubMed ID : 23250415
- Web of Science ID : WOS:000316356700052