Significance for epigenomic regulation of renal gene expressions in the onset of salt-induced hypertension.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09735
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: MIYASHITA Kazutoshi 慶應義塾大学, 医学部(信濃町), 特任准教授 (50378759)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 高血圧 / 塩分負荷 / 高血圧自然発症ラット / 記憶現象 / エピゲノム / ヒストンアセチル化 / 腎細動脈 / MMP2

Outline of Final Research Achievements

We found a salt memory phenomenon in which spontaneously hypertensive rats (SHR) were subjected to transient salt loading and the systolic blood pressure was persistently increased even after discontinuation of the salt loading. In the present study, we investigated the significance for epigenetic modification of chromatin in persistent increase in the blood pressure after salt loading. Following transient salt loading, renal arteriole-specific epigenetic alterations persist, and histone acetylation-mediated MMP2 upregulation in the renal arterioles might promote medial hypertrophy which lead to renin hypersecretion and persistent elevation in the blood pressure.

Free Research Field

内分泌学、代謝学、高血圧学

Academic Significance and Societal Importance of the Research Achievements

申請者の研究室では、高血圧自然発症ラット(SHR)に一過性の塩分負荷を与えると、塩分負荷中止後も血圧が持続的に上昇することを見出し、腎細動脈の中膜肥厚に伴うレニン分泌の亢進が、血圧上昇の本態となる可能性を指摘した[Oguchi Hypertension. 2014]。本研究では腎臓のエピゲノム変容について解析し、塩分負荷に伴う腎細動脈リモデリングや、Na輸送の変容に関与するクロマチンエピゲノム修飾を同定した。この知見は、腎のエピゲノム変容を治療標的とした、新しい高血圧治療戦略の開発につながるものである。