Department of Cardiology and Angiology, University Heart Center Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Institute of Anatomy, University of Veterinary Medicine of Hannover, Foundation, 30173 Hannover, Germany.
Int J Mol Sci. 2022 Sep 3;23(17):10075. doi: 10.3390/ijms231710075.
The eukaryotic initiation factor 4E binding protein (4E-BP) family is involved in translational control of cell proliferation and pro-angiogenic factors. The zebrafish eukaryotic initiation factor 4E binding protein 3 like () is a member of the 4E-BPs and responsible for activity-dependent myofibrillogenesis, but whether it affects cardiomyocyte (CM) proliferation or heart regeneration is unclear. We examined during zebrafish vascular development and heart regeneration post cryoinjury in adult zebrafish. Using morpholino injections we induced silencing of in zebrafish embryos, which led to increased angiogenesis at 94 h post fertilization (hpf). For investigation of in cardiac regeneration, zebrafish hearts were subjected to cryoinjury. Regenerating hearts were analyzed at different time points post-cryoinjury for expression of by in situ hybridization and showed strongly decreased expression in the injured area. We established a transgenic zebrafish strain, which overexpressed under the control of a heat-shock dependent promotor. Overexpression of during zebrafish heart regeneration caused only macroscopically a reduced amount of fibrin at the site of injury. Overall, these findings demonstrate that silencing of has pro-angiogenic properties in zebrafish vascular development and when is overexpressed, fibrin deposition tends to be altered in zebrafish cardiac regeneration after cryoinjury.
真核起始因子 4E 结合蛋白（4E-BP）家族参与细胞增殖和促血管生成因子的翻译控制。斑马鱼真核起始因子 4E 结合蛋白 3 样物（）是 4E-BP 的一员，负责活性依赖性肌原纤维发生，但它是否影响心肌细胞（CM）增殖或心脏再生尚不清楚。我们在成年斑马鱼中检查了血管发育过程中的和心脏再生后冷冻损伤。通过注射 morpholino，我们在斑马鱼胚胎中诱导沉默，导致受精后 94 小时（hpf）时血管生成增加。为了研究在心脏再生中的作用，我们对斑马鱼心脏进行了冷冻损伤。在损伤后不同时间点通过原位杂交分析再生心脏中 的表达，发现损伤区域 的表达明显降低。我们建立了一种转基因斑马鱼品系，该品系在热休克依赖启动子的控制下过表达。在斑马鱼心脏再生过程中过表达 仅导致损伤部位的纤维蛋白含量宏观上减少。总的来说，这些发现表明在斑马鱼血管发育中沉默 具有促血管生成特性，而过表达 时，冷冻损伤后斑马鱼心脏再生中的纤维蛋白沉积倾向于发生改变。
