Cytoskeleton alteration regulates cardiomyocyte cell cycle activity and histone modification via Sirt1-NFAT axis
The acquisition of knowledge pertaining to the molecular mechanisms that govern cardiomyocyte (CM) proliferation would enable the creation of novel approaches to promote cardiac regeneration in adult individuals, a crucial therapeutic objective that has yet to be accomplished. The limited regenerative response observed in adult myocardium may be attributed, in part, to the relatively low proliferative capacity of cardiomyocytes. The comprehension of cardiomyocyte division is a complex undertaking, as cardiomyocytes are capable of entering the cell cycle but are unable to complete cell division. Our research revealed that the induction of cardiac cytoskeleton changes by Blebbistatin result in the entry of cardiomyocytes entry into the cell cycle but, followed by cell cycle arrest at the G2/M phase. Sirt1 is identified as a potential mediator of the binucleation process in neonatal rat cardiomyocytes, which is regulated by the cardiomyocyte cytoskeleton. Furthermore, the distribution of H3K9me3 in cardiomyocytes with varying nuclear numbers and treatments indicates a significant involvement in the formation of binucleated cardiomyocytes. Overall design: To investigate what mediate the cytoskeleton alters epigenetics in cardiomyocytes,we treated neonatal rat ventricular cardiomyocytes with 25µm blebbistatin or DMSO for 0.5h. RNA-seq analysis of NRVCs treated with 0.25µm Blebb or DMSO; ChIP-Seq analysis of H3K9me3 in NRVCs treated with 0.25µm Blebb or DMSO(3 replicates per group).