Zebrafish have a remarkable ability to regenerate the myocardium after injury by proliferation of pre-existing cardiomyocytes. Fibroblast growth factor (FGF) signaling is known to play a critical role in zebrafish heart regeneration through promotion of neovascularization of the regenerating myocardium. Here, we define an additional function of FGF signaling in the zebrafish myocardium after injury. We find that FGF signaling is active in a small fraction of cardiomyocytes before injury, and that the number of FGF signaling-positive cardiomyocytes increases after amputation-induced injury. We show that ERK phosphorylation is prominent in endothelial cells, but not in cardiomyocytes. In contrast, basal levels of phospho-AKT positive cardiomyocytes are detected before injury, and the ratio of phosphorylated AKT-positive cardiomyocytes increases after injury, indicating a role of AKT signaling in cardiomyocytes following injury. Inhibition of FGF signaling reduced the number of phosphorylated AKT-positive cardiomyocytes and increased cardiomyocyte death without injury. Heart injury did not induce cardiomyocyte death; however, heart injury in combination with inhibition of FGF signaling caused significant increase in cardiomyocyte death. Pharmacological inhibition of AKT signaling after heart injury also caused increased cardiomyocyte death. Our data support the idea that FGF-AKT signaling-dependent cardiomyocyte survival is necessary for subsequent heart regeneration.

斑马鱼通过预先存在的心肌细胞的增殖在损伤后具有显着的心肌再生能力。已知成纤维细胞生长因子 (FGF) 信号通过促进再生心肌的新血管形成在斑马鱼心脏再生中发挥关键作用。在这里，我们定义了损伤后斑马鱼心肌中 FGF 信号传导的附加功能。我们发现 FGF 信号传导在损伤前一小部分心肌细胞中是活跃的，并且 FGF 信号传导阳性心肌细胞的数量在截肢引起的损伤后增加。我们表明 ERK 磷酸化在内皮细胞中很突出，但在心肌细胞中则不然。相反，在损伤前检测到磷酸化AKT阳性心肌细胞的基础水平，并且磷酸化AKT阳性心肌细胞的比例在损伤后增加，表明AKT信号传导在损伤后心肌细胞中的作用。抑制 FGF 信号可减少磷酸化 AKT 阳性心肌细胞的数量，并增加心肌细胞无损伤死亡。心脏损伤不会导致心肌细胞死亡；然而，心脏损伤与 FGF 信号传导的抑制相结合导致心肌细胞死亡显着增加。心脏损伤后对 AKT 信号的药理学抑制也导致心肌细胞死亡增加。我们的数据支持这样一种观点，即 FGF-AKT 信号依赖的心肌细胞存活对于随后的心脏再生是必要的。抑制 FGF 信号可减少磷酸化 AKT 阳性心肌细胞的数量，并增加心肌细胞无损伤死亡。心脏损伤不会导致心肌细胞死亡；然而，心脏损伤与 FGF 信号传导的抑制相结合导致心肌细胞死亡显着增加。心脏损伤后对 AKT 信号的药理学抑制也导致心肌细胞死亡增加。我们的数据支持这样一种观点，即 FGF-AKT 信号依赖的心肌细胞存活对于随后的心脏再生是必要的。抑制 FGF 信号可减少磷酸化 AKT 阳性心肌细胞的数量，并增加心肌细胞无损伤死亡。心脏损伤不会导致心肌细胞死亡；然而，心脏损伤与 FGF 信号传导的抑制相结合导致心肌细胞死亡显着增加。心脏损伤后对 AKT 信号的药理学抑制也导致心肌细胞死亡增加。我们的数据支持这样一种观点，即 FGF-AKT 信号依赖的心肌细胞存活对于随后的心脏再生是必要的。心脏损伤后对 AKT 信号的药理学抑制也导致心肌细胞死亡增加。我们的数据支持这样一种观点，即 FGF-AKT 信号依赖的心肌细胞存活对于随后的心脏再生是必要的。心脏损伤后对 AKT 信号的药理学抑制也导致心肌细胞死亡增加。我们的数据支持这样一种观点，即 FGF-AKT 信号依赖的心肌细胞存活对于随后的心脏再生是必要的。