Revealing the regulatory mechanism of the natriuretic peptides and developing the new therapy for heart failure

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21315
• Project/Area Number (Other): 18H06212 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Osaka University
• Principal Investigator: Matsuoka Ken 大阪大学, 医学系研究科, 助教 (90826190)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: CR9 / エンハンサー / 心不全 / ナトリウム利尿ペプチド

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 revealed that the CR9 enhancer was induced by pharmacological and mechanical stimulations in both cultured cardiomyocytes and in-vivo murine hearts.

Free Research Field

医学

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。