Molecular mechanism of cardiac regeneration

Neonatal mammalian heart has recently been shown to possess the capacity to regenerate completely after injury. This remarkable regenerative capacity is lost after postnatal day 7. This transition has been marked with cardiomyocyte cell cycle arrest and induction of fibrotic response similar to what occurs after myocardial infarction in adults. We have recently outlined the function of Meis1 as a new cardiogenic factor that plays a pivotal role in neonatal cardiac regeneration. However, underlying molecular mechanisms of neonatal cardiac regeneration and other cardiogenic factors remained elusive. Here, we investigated the involvement of novel putative cardiogenic factors in neonatal cardiac regeneration and cardiomyocyte cell cycle withdrawal. We have confirmed their expression in the heart and cardiomyocytes. We have shown that expressions of Inpp5d, Dnmt3a, c-Myc and Cbl are significantly downregulated during neonatal cardiac regeneration process. Intriguingly, these four factors are upregulated in non-regenerative period of 7-day old mice after injury. Taken together, our findings suggest that Inpp5d, Dnmt3a, c-Myc and Cbl may be involved in the regulation of cardiomyocyte cell cycle progression and represent new targets for induction of cardiac regeneration.