de Preux Charles Anne-Sophie, Bise Thomas, Baier Felix, Marro Jan, Jaźwińska Anna
Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland
Open Biol. 2016 Jul;6(7). doi: 10.1098/rsob.160102.
The adult heart is able to activate cardioprotective programmes and modifies its architecture in response to physiological or pathological changes. While mammalian cardiac remodelling often involves hypertrophic expansion, the adult zebrafish heart exploits hyperplastic growth. This capacity depends on the responsiveness of zebrafish cardiomyocytes to mitogenic signals throughout their entire life. Here, we have examined the role of inflammation on the stimulation of cell cycle activity in the context of heart preconditioning and regeneration. We used thoracotomy as a cardiac preconditioning model and cryoinjury as a model of cardiac infarction in the adult zebrafish. First, we performed a spatio-temporal characterization of leucocytes and cycling cardiac cells after thoracotomy. This analysis revealed a concomitance between the infiltration of inflammatory cells and the stimulation of the mitotic activity. However, decreasing the immune response using clodronate liposome injection, PLX3397 treatment or anti-inflammatory drugs surprisingly had no effect on the re-entry of cardiac cells into the cell cycle. In contrast, reducing inflammation using the same strategies after cryoinjury strongly impaired cardiac cell mitotic activity and the regenerative process. Taken together, our results show that, while the immune response is not necessary to induce cell-cycle activity in intact preconditioned hearts, inflammation is required for the regeneration of injured hearts in zebrafish.
成年心脏能够激活心脏保护程序，并根据生理或病理变化改变其结构。虽然哺乳动物的心脏重塑通常涉及肥大性扩张，但成年斑马鱼的心脏利用增生性生长。这种能力取决于斑马鱼心肌细胞在其整个生命周期中对有丝分裂信号的反应能力。在此，我们研究了炎症在心脏预处理和再生背景下对细胞周期活性刺激的作用。我们将开胸手术用作成年斑马鱼心脏预处理模型，将冷冻损伤用作心脏梗死模型。首先，我们对开胸手术后的白细胞和处于细胞周期的心脏细胞进行了时空特征分析。该分析揭示了炎症细胞浸润与有丝分裂活性刺激之间的同步性。然而，使用氯膦酸脂质体注射、PLX3397处理或抗炎药物降低免疫反应，令人惊讶的是对心脏细胞重新进入细胞周期没有影响。相反，在冷冻损伤后使用相同策略减轻炎症会严重损害心脏细胞的有丝分裂活性和再生过程。综上所述，我们的结果表明，虽然免疫反应对于在完整的预处理心脏中诱导细胞周期活性不是必需的，但炎症是斑马鱼受伤心脏再生所必需的。
