Salt stress-induced responses in health and disease: the role of WNK kinases and new therapeutic strategies

2017 Fiscal Year Final Research Report

• Project/Area Number: 25221306
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: UCIDA Shinichi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50262184)
• Co-Investigator(Renkei-kenkyūsha): SASAKI Sei 東京医科歯科大学, 大学院医歯学総合研究科, 名誉教授 (60170677)
• Project Period (FY): 2013-05-31 – 2018-03-31
• Keywords: キナーゼ / 腎臓 / 塩分感受性高血圧 / メタボリックシンドローム / ケミカルライブラリー

Outline of Final Research Achievements

To elucidate the effects of salt loading to the living organism, we started with investigating the WNK signaling system. Since the WNK signal is a recently discovered, novel regulatory system with most of its functions unknown, we first sought to elucidate its roles in each organ, to clarify its regulatory mechanisms, and to identify downstream target molecules. As a result, we have revealed that, in addition to its role in renal sodium handling, the WNK signal plays important roles in various tissues such as regulation of blood pressure via tonus regulation in vascular smooth muscle, adipocyte and myocyte differentiation, and control of immunological response. Next, we have shown how its dysregulation can lead to pathological consequences in response to salt loading or kidney injury. Moreover, we have established a unique chemical compound screening system and obtained promising drug seeds to regulate WNK signaling, paving the way for developing novel therapeutic intervention.

Free Research Field

腎臓内科学