• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2020 Fiscal Year Final Research Report

Investigation of a novel function of WNK signal in macrophage

Research Project

  • PDF
Project/Area Number 19K16686
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49070:Immunology-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Arai Yohei  東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (40824339)

Project Period (FY) 2019-04-01 – 2021-03-31
KeywordsWNK / マクロファージ / サイトカイン / 敗血症
Outline of Final Research Achievements

With-no-lysine kinase (WNK) plays important roles in regulating electrolyte homeostasis, cell signaling, survival, and proliferation. It has been recently demonstrated that WNK1 modifies the function of immune cells. Here we clarified that in macrophages, WNK1 has suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses via TGFβ-activated kinase 1 (TAK1)-mediated activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway. Moreover, we found that WNK1 heterozygous mice produced excessive proinflammatory cytokines in an experimental LPS-induced sepsis model. These results suggest that WNK1 acts as a physiologic immune modulator via interactions with TAK1. WNK1-TAK1 signaling pathway may be a therapeutic target against the cytokine storm caused by sepsis.

Free Research Field

腎臓内科学、免疫学、分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

生体の防御機構として働く炎症シグナルが何らかの原因で亢進してサイトカインが過剰に産生されると、致死的なサイトカインストームという病態が引き起こされるが、この病態に対する根本的な治療法は確立されていない。本研究は、WNKキナーゼという新たな視点からWNK1-TAK1シグナル伝達経路が、生体においてもLPS誘導性の炎症シグナルのnegative feedback機構として働く新たな分子機構であることを明らかにした。今後さらなる研究によってWNK1-TAK1シグナル伝達経路をターゲットとした新たな治療戦略を提案することを目指していきたい。

URL: 

Published: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi