Elucidation of the molecular mechanism for the development of salt sensitive hypertension by serine proteases.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591231
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: ADACHI Masataka 熊本大学, 医学部附属病院, 助教 (90398206)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 高血圧 / 上皮型ナトリウムチャネル / セリンプロテアーゼ / セリンプロテアーゼ阻害薬

Outline of Final Research Achievements

Aldosterone induces a molecular weight shift of the epithelial sodium channel γ subunit (γENaC) from 85 to 70 kDa that is necessary for the channel activation. However, the in vivo contribution of serine proteases to this cleavage still remains unclear. To address this issue, we administrated a synthetic serine protease inhibitor camostat mesilate (CM) to aldosterone-infused rats. CM decreased the abundance of 70 kDa form of ENaC.Our findings strongly indicate that CM inhibited the cleavage of γENaC by prostasin and subsequently suppressed the ENaC activity. The results of our current studies also suggest the possibility that a synthetic serine protease inhibitor CM might represent a new strategy for the treatment of salt-sensitive hypertension in humans.

Free Research Field

腎臓内科学