Overexpression of Gopc Promotes Cardiomyocyte Proliferation but Delays Overall Heart Regeneration in Zebrafish

The adult mammalian heart exhibits minimal regenerative capacity as cardiomyocytes are quiescent, whereas the adult zebrafish robustly regenerates injured myocardium. Understanding the mechanisms of this natural cardiac regeneration capacity may inform strategies to stimulate cardiomyocyte proliferation in adult mammals. The Golgi apparatus plays a critical role within the cardiovascular system. Here, we identified a Golgi-associated protein, Gopc, as a novel regulator of myocardial proliferation and regeneration in zebrafish. Sequence alignment and phylogenetic analysis showed high conservation of Gopc from zebrafish to humans. In zebrafish, its transcript is highly expressed in cardiomyocytes following cardiac injury. To elucidate the impact of Gopc on cardiac regeneration, we established a transgenic zebrafish model with gopc overexpression specifically in cardiomyocytes. Under uninjured conditions, this transgenic fish possesses increased cardiomyocyte proliferation compared to wild-type fish. At 7 days post-amputation (dpa), the cardiomyocyte proliferation at the injury site remains higher in transgenic fish than in wild-type fish. However, at 30 dpa, compared to the control fish, the myocardial regeneration in the transgenic fish is delayed, accompanied by substantial scar tissue at the amputation site. Coronary endothelial tube regeneration also exhibits a corresponding delay, which may contribute to the impaired cardiac regeneration observed. Taken together, our data identify Gopc as a critical modulator that uncouples cardiomyocyte proliferation from the later stages of regenerative resolution, expanding our understanding of cardiac regeneration mechanisms and highlighting the necessity of balanced regulation across distinct phases of the healing process.