Regulation of MR activity by a novel transcriptional coactivator, LSD1, and its significance in the development of salt-sensitive hypertension

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Keio University
• Principal Investigator: KOBAYASHI Sakiko 慶應義塾大学, 医学部(信濃町), 特任講師 (80383727)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 食塩感受性高血圧 / MR / 転写共役因子 / LSD1 / 高血圧

Outline of Final Research Achievements

In short-term aldosterone administration experiments, renal tubule-specific LSD1 knockout mice (KspLSD1-KO) showed a significantly stronger increase in the expression of ENaCα than control mice, suggesting increased aldosterone sensitivity. KspLSD1-KO mice showed a significant increase in blood pressure compared to control mice, which disappeared after administration of MR antagonist (spironolactone). Strong fibrosis was observed in both groups, but was suppressed by spironolactone to the same extent as in the normal diet; there was a strong tendency toward fibrosis in KspLSD1-KO, suggesting increased aldosterone sensitivity.

Free Research Field

内分泌内科

Academic Significance and Societal Importance of the Research Achievements

本研究ではエピゲノム修飾因子の1つであるLSD1がMRのcorepressorとして機能し、MR作用を介し食塩感受性高血圧の発症リスクに関与していることが示された。本研究の成果はLSD1のエピゲノム修飾因子としての新たな機能を明らかにしたのみならず、これまで疫学的に示唆されていたLSD1と食塩感受性の背景にある分子機序を明らかにした点で価値が高いと考えられるた。