The role of the FUBP1 protein in the regulation of maturation and hypertrophic growth of cardiomyocytes.

• Grant number: 25/02227-0
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Alisson Campos Cardoso
• Grantee: Alisson Campos Cardoso
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated researchers: Ana Helena Macedo Pereira

Abstract

Heart failure is a costly and deadly disease, affecting over 64 million people worldwide. At the core of the pathophysiology of heart failure is the inability of the adult mammalian heart to regenerate after injury. In contrast to the adult heart, the neonatal mammalian heart is capable of complete regeneration without significant hypertrophy or fibrosis. This regenerative capacity is mediated by the proliferation of preexisting cardiomyocytes and is lost by 7 days after birth, after which most postnatal cardiomyocytes become binucleated, undergo cell cycle arrest, and begin the process of maturation and growth by hypertrophy. Recent studies indicate that the protein FUBP1 (Far Upstream Binding Protein 1) plays a critical role in the regulation of the cell cycle and hypertrophic growth of cardiomyocytes. Germline knockout mice for Fubp1 (Fubp1-/-) have shown embryonic lethality from day 10.5. Phenotypically, these animals exhibited a small body size associated with hypoplasia of multiple organs, except for the heart, which presented concentric cardiac hypertrophy. However, the molecular mechanisms regulated by FUBP1 in the remodeling and hypertrophic growth of the heart are still poorly understood. This project aims to investigate the role of FUBP1 in the maturation of postnatal cardiomyocytes and in the regulation of hypertrophic growth, using cellular and murine models. Through gene editing techniques, transcriptomic and proteomic analyses, we will evaluate the effects of FUBP1 deletion or overexpression on metabolic pathways, survival, and cardiac development. The results of this study may provide new insights into the regulatory mechanisms of growth, differentiation and cell cycle progression of cardiomyocytes and potential therapeutic targets for heart diseases. (AU)