Establishment of a Reprogramming Method for Cardiomyocyte Proliferation by Targeting Nucleic Acid Metabolism

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15356
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Saito Yuichi 国立研究開発法人理化学研究所, 生命機能科学研究センター, 基礎科学特別研究員 (30880364)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: キサンチン代謝 / プリン代謝 / 心筋再生 / 心筋増殖停止 / 酸化DNA損傷

Outline of Final Research Achievements

Following birth, the cardiomyocytes in mammals face exposure to environments rich in oxygen, leading to oxidative damage to their DNA. This damage significantly impairs their ability to proliferate and regenerate, permanently. Consequently, adult mammalian cardiomyocytes generally lack the ability to regenerate. However, it's been observed that extended exposure to conditions of low oxygen can restore their capacity to proliferate. Nonetheless, using long-term hypoxia as a treatment for heart attacks is impractical. There's a growing interest in developing a drug-based approach for the proliferative reprogramming of cardiomyocytes, although success has been elusive. This research aims to discover such a method by manipulating the metabolism of nucleic acids, essential DNA components, towards proliferative reprogramming.

Free Research Field

再生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、心筋再生能力の再賦活化という臨床的意義のある新たな治療戦略を確立するために重要な心筋増殖停止および心筋再生能力喪失の分子基盤についてのエビデンスを得るものである。本研究成果により、これまで心筋増殖能力の喪失および心筋再生能力の喪失と結び付けられることのなかった核酸塩基代謝の新たな役割が見出された。