iScience. 2025 May 22;28(7):112724. doi: 10.1016/j.isci.2025.112724. eCollection 2025 Jul 18.
ABSTRACT
Mammalian cardiomyocytes are arrested from the cell cycle shortly after birth, and therefore mammals lose the ability to regenerate injured myocardium for the rest of their lives. Pharmacological induction of cardiomyocyte proliferation has gained a lot of interest in recent years, as researchers strive to achieve heart tissue regeneration. Here, we show that a small chemical, benzyl isothiocyanate (BITC), induced cardiomyocyte proliferation through activation of the mitogen-activated protein kinase (MAPK) pathway. BITC treatment also allowed heart regeneration in the infarcted neonatal heart, even after the regeneration period in mice. Furthermore, administration of BITC to adult mice in parallel with mild hypoxia (10% O2) induced cell cycle reentry and tissue regeneration in the adult heart. Our findings thus suggest that pharmacological activation of the MAPK pathway using BITC, concurrently with the activation of hypoxia-related signaling pathways, may be a promising approach to inducing cardiac regeneration in patients with heart disease.
PMID:40585362 | PMC:PMC12205616 | DOI:10.1016/j.isci.2025.112724
