Persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopy-guided heart resection in adult Xenopus.
Persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopy-guided heart resection in adult Xenopus.
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DOI：
10.1371/journal.pone.0173418
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Chai N
中科院分区：
文献类型：
--
作者：
Marshall L;Vivien C;Girardot F;Péricard L;Demeneix BA;Coen L;Chai N
需要心脏修复模型来了解人类心脏组织再生失败的机制。目前，这类研究主要使用斑马鱼和老鼠。值得注意的是，正是在这两个进化分离的物种之间，成人心脏再生能力被认为是丧失的，但这种差异的原因在很大程度上仍不清楚。处于这两种模式之间进化位置的两栖动物，特别感兴趣的是帮助填补这种知识的缺乏。因此，我们开发了一种基于内窥镜的切除方法，以探索成年非洲爪哇心脏损伤的后果。这种方法允许原位活体心脏观察，标准化的组织截肢大小和重复性。在截肢后第一周，细胞增殖标记物的基因表达没有变化，而与肌节组织有关的基因表达减少，炎症、纤维化和肥大的标记物增加。截肢后1个月，损伤部位有明显的纤维化和肥大，持续11个月。此外，心肌细胞肌节组织在截肢后早期恶化，直到11个月后仍未完全恢复。我们得出结论，成年非洲爪哇心脏不能再生，显示出疤痕形成的细胞和分子标记。我们的工作表明，与尾龙和硬骨鱼相反，除了青蛙之外，成年无尾两栖动物的心脏损伤结果与成年哺乳动物相似。这一观察结果与目前认为心脏再生能力丧失与获得恒温有关的假设是不一致的。
Models of cardiac repair are needed to understand mechanisms underlying failure to regenerate in human cardiac tissue. Such studies are currently dominated by the use of zebrafish and mice. Remarkably, it is between these two evolutionary separated species that the adult cardiac regenerative capacity is thought to be lost, but causes of this difference remain largely unknown. Amphibians, evolutionary positioned between these two models, are of particular interest to help fill this lack of knowledge. We thus developed an endoscopy-based resection method to explore the consequences of cardiac injury in adult Xenopus laevis. This method allowed in situ live heart observation, standardised tissue amputation size and reproducibility. During the first week following amputation, gene expression of cell proliferation markers remained unchanged, whereas those relating to sarcomere organisation decreased and markers of inflammation, fibrosis and hypertrophy increased. One-month post-amputation, fibrosis and hypertrophy were evident at the injury site, persisting through 11 months. Moreover, cardiomyocyte sarcomere organisation deteriorated early following amputation, and was not completely recovered as far as 11 months later. We conclude that the adult Xenopus heart is unable to regenerate, displaying cellular and molecular marks of scarring. Our work suggests that, contrary to urodeles and teleosts, with the exception of medaka, adult anurans share a cardiac injury outcome similar to adult mammals. This observation is at odds with current hypotheses that link loss of cardiac regenerative capacity with acquisition of homeothermy.