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2019 Fiscal Year Final Research Report

Development of novel preventive drugs for lifestyle disease by inhibiting WNK4 signaling

Research Project

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Project/Area Number 18K19534
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Shinichi Uchida  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50262184)

Project Period (FY) 2018-06-29 – 2020-03-31
KeywordsWNKシグナル / 生活習慣病 / 塩分感受性高血圧 / メタボリック症候群 / 創薬 / 炎症性サイトカイン / TNFα
Outline of Final Research Achievements

We focused on the role of WNK kinase signaling, which plays an important role in sodium handling and blood pressure control, and tried to seek the substrate of WNK4 in adipocytes, but no promising candidate was so far obtained unfortunately. Subsequently, we hypothesized that WNK kinase is a factor that links increased inflammatory cytokines and salt-sensitive hypertension in metabolic syndrome (MetS) or chronic kidney disease (CKD), and examined three types of CKD model mice. As a result, the WNK signal was observed to be enhanced in these kidneys and to be activated by TNFα. This was considered to be responsible for part of the mechanism of salt sensitive hypertension in MetS or CKD. The result was reported in Kidney International (IF: 8.4).

Free Research Field

腎臓病・高血圧症

Academic Significance and Societal Importance of the Research Achievements

これまでの我々の研究成果から、WNKシグナル伝達系の制御は塩分感受性高血圧症にとどまらず肥満、耐糖能異常といったメタボリック症候群(MetS)に対する包括的治療標的となり得る可能性が期待される。今回明らかにした炎症性サイトカインとWNKシグナル伝達系との相関関係は、創薬ターゲットとしてのWNKシグナル制御の妥当性をさらに支持するものであり、有用な知見と考えられる。

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Published: 2021-02-19  

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