Elucidation of regulatory mechanism of aldosterone synthesis based on ER chaperone

• Project/Area Number: 17H06893
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Hiroshima University
• Principal Investigator: Itcho Kiyotaka 広島大学, 病院(医), 助教 (00805666)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 循環器 / 高血圧 / 循環器・高血圧

Outline of Final Research Achievements

Primary aldosteronism, which is a the most common form of secondary hypertension, leads to cardiovascular disease and renal dysfunction by excess aldosterone secretion. This study revealed that ER chaperone calmegin (CLGN) was up-regulated in aldosterone producing adenoma and CLGN up-regulated aldosterone synthesis (CYP11B2) by translational regulation. These findings could be useful for the development of agents of targeting aldosterone production.

Academic Significance and Societal Importance of the Research Achievements

原発性アルドステロン症 (PA) は高血圧患者の5-10%程度を占め，極めて頻度の高い疾患である．アルドステロン過剰分泌により，高血圧を来すだけではなく心血管疾患や腎機能障害を高率に合併するため，PAの診断・治療およびアルドステロン合成の制御は極めて重要である．しかしPAの診断は複数回の煩雑な検査や入院精査を必要とし，アルドステロン合成を直接阻害する薬剤は現在までない．本研究成果はPAや高血圧に対する新しい診断や治療戦略の開発に役立つ可能性がある．

Research Products

• [Presentation] Molecular chaperone CLGN associates with aldosterone production in APA and APCC. (2019)
  • Author(s): Kiyotaka Itcho, Kenji Oki, Celso E. Gomez-Sanchez, Elise P. Gomez-Sanchez, Kazuhiro Kobuke, Ryuta Baba, Haruya Ohno, Masayasu Yoneda, Noboru Hattori
  • Organizer: 44th Meeting of the International Aldosterone Meeting
  • Int'l Joint Research
• [Presentation] 分子シャペロンCLGNはアルドステロン産生腫瘍に特異的に発現しアルドステロン合成に関与する (2019)
  • Author(s): 一町澄宜，沖健司，馬場隆太，小武家和博，大久保博史，大野晴也，米田真康
  • Organizer: 第92回日本内分泌学会学術総会
• [Presentation] Molecular chaperone Calmegin is up-regulated in aldosterone-producing adenoma and associates with aldosterone production. (2018)
  • Author(s): Kiyotaka Itcho
  • Organizer: 43rd Meeting of the International Aldosterone Conference
  • Int'l Joint Research