Dynamic microRNA-101a and Fosab expression controls zebrafish heart regeneration

摘要: Cardiovascular disease is the leading cause of morbidity and mortality in Western world owing to limited regenerative capacity mammalian cardiovascular system. In lieu new muscle synthesis, human heart replaces necrotic tissue with deposition a noncontractile scar. By contrast, adult zebrafish endowed remarkable capacity, capable de novo cardiomyocyte (CM) creation scar removal when challenged an acute injury. these studies, we examined contributions dynamically regulated microRNA miR-101a during regeneration. We demonstrate that expression rapidly depleted within 3 days post-amputation (dpa) but highly upregulated by 7-14 dpa, before returning uninjured levels at completion process. Employing heat-inducible transgenic strains antisense oligonucleotides, decreases onset cardiac injury enhanced CM proliferation. Interestingly, prolonged suppression activity stimulates synthesis defects clearance. Upregulation between 7 14 dpa essential stimulate Through series identified proto-oncogene fosab (cfos) as potent target gene, stimulator proliferation, inhibitor removal. Importantly, combinatorial depletion rescued clearance mediated inhibition alone. summation, our studies indicate precise temporal modulation miR-101a/fosab genetic axis crucial for coordinating proliferation