Exploratory research of treatment target or marker for aldosterone producing adenoma by using of metabolome analysis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17600
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Hiroshima University
• Principal Investigator: Kobuke Kazuhiro 広島大学, 医系科学研究科(医), 寄附講座助教 (80805648)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 原発性アルドステロン症 / メタボローム / 二次性高血圧 / 腫瘍形成

Outline of Final Research Achievements

We introduced the ATP1A1 gene mutation, one of the somatic gene mutations found in aldosterone-producing adenoma (APA), into adrenal carcinoma cell lines to obtain an APA model cell line. We performed RNA-Seq and metabolome analysis of these model cells to analyze changes in gene expression and intracellular metabolism. The results suggest that nucleic acid synthesis is enhanced in APA with ATP1A1 mutation, which, together with the change in gene expression in RNA-Seq, indicates activation of cell proliferation, suggesting that ATP1A1 mutation in adrenocortical cells promotes cell proliferation and triggers APA tumorigenesis. The results suggest that the ATP1A1 mutation in adrenocortical cells promotes cell proliferation and may trigger APA tumor formation.

Free Research Field

高血圧

Academic Significance and Societal Importance of the Research Achievements

原発性アルドステロン症（PA)は難治性の二次性高血症の原因となり，高頻度に動脈硬化性疾患を合併することから，この疾患克服は国民の生命予後，ならびに生活の質の向上のために重要である．PAの原因の多くを占めるアルドステロン産生腺腫（APA）において，疾患克服に向けて，病因となる分子メカニズムの解明が多数試みられており，アルドステロン産生機構への理解は深まりつつある．しかしながらAPAの腫瘍形成機構の解明につながる知見は未だ少なく，今回の知見を踏まえ，APA腫瘍形成の分子メカニズムが明らかになっていけば，将来のAPA治療，あるいは予防につながる発見にも発展し得ると考えられる．