Clarification of the transcriptional regulatory mechanism of natriuretic peptides in failing hearts

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17151
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Osaka University
• Principal Investigator: Matsuoka Ken 大阪大学, 医学系研究科, 助教 (90826190)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: CR9 / エンハンサー / 心不全 / ナトリウム利尿ペプチド / 遺伝子治療

Outline of Final Research Achievements

The natriuretic peptides, atrial natriuretic peptide (ANP) and brain　natriuretic peptide (BNP), encoded by the neighboring genes are well-known biomarkers that are strongly induced during heart failure and represent its severity. Cardiologists frequently use these peptides as natriuretic and vasorelaxant agents to treat various clinical conditions. We identified 650bp of heart-failure responsive enhancer (CR9) inducing ANP/BNP gene expressions in the previous study. However, the regulatory mechanism of CR9 remains unknown. In the present study, we generated CR9 knockout mice and revealed the transcriptional regulatory mechanism of CR9 in failing hearts.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

ANP/BNPは心不全病態に非常に特異性高く発現誘導される生理活性ペプチドであり、ヒトでは既に血清で測定可能な心不全重症度指標として、また心不全治療薬として頻用されている、有望な分子標的である。本研究は我々が有する先行知財を用い、不全心におけるANP/BNP転写制御機構の解明を目的とした一貫した研究であり、心不全病態解明・新規心不全治療薬に繋がる大きな意義を有する。