HEART REGENERATION IS REGULATES BY KEY MICRO RNAs FROM FISH TO MAMMALS: what it can learned about the epicardial cells activation during the regeneration in zebrafish

Zebrafish could be an interesting translational model to understand and improve the post-infarction trial and possible regeneration in mammals. The regenerative capacity in mammalian heart is maintained partially in neonatal life1 because are still switch-on some phylogenetic-conserved genes; while in adult, it seems to confined in replacing by a few of cardiomyocytes (CM) and by a large amount of fibroblasts2,3. In contrast, natural cardiac regeneration appears to be excellent in fish after an injury. In zebrafish, the cardiac environment created by cardiomyocytes, fibroblasts, and non-muscle cells after injury is believed to be critical in facilitating the regenerative response4. The epicardium-derived cells and the consequent epicardial cells (EPCs) are essential regulators since they respond to FGFs in both embryogenesis and regeneration processes. EPCs undergo to number of cellular modifications5,6 that is required to silenced by miRs that controlled the differentiation of the cells. This downregulation is a necessary event to activate the transition from epithelial to mesenchymal cells, such as cytoskeletal re-arrange and expression of hyaluronan-mediated motility receptor, necessaries to move in the damage site7,8. In the heart several molecules are involved in the protein synthesis regulation9 where the miRs have a upstream actions. MiR1 and miR133 (a and b) are involved in the activation of fibroblasts in producing FGFs10,11, as well as the hypertrophic response of epithelial and muscular cells after injury, to compensate for the loss-of-contractile tissue in mammals, as well as in zebrafish9,12,13,14.