Shanghai Key Laboratory of Regulatory Biology, Institute of Molecular Medicine, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510100, Guangdong, China.
Curr Cardiol Rep. 2022 Oct;24(10):1425-1438. doi: 10.1007/s11886-022-01756-8. Epub 2022 Aug 4.
Cardiovascular diseases are the leading cause of death worldwide, largely due to the limited regenerative capacity of the adult human heart. In contrast, teleost zebrafish hearts possess natural regeneration capacity by proliferation of pre-existing cardiomyocytes after injury. Hearts of mice can regenerate if injured in a few days after birth, which coincides with the transient capacity for cardiomyocyte proliferation. This review tends to elaborate the roles and mechanisms of Wnt/β-catenin signaling in heart development and regeneration in mammals and non-mammalian vertebrates.
Studies in zebrafish, mice, and human embryonic stem cells demonstrate the binary effect for Wnt/β-catenin signaling during heart development. Both Wnts and Wnt antagonists are induced in multiple cell types during cardiac development and injury repair. In this review, we summarize composites of the Wnt signaling pathway and their different action routes, followed by the discussion of their involvements in cardiac specification, proliferation, and patterning. We provide overviews about canonical and non-canonical Wnt activity during heart homeostasis, remodeling, and regeneration. Wnt/β-catenin signaling exhibits biphasic and antagonistic effects on cardiac specification and differentiation depending on the stage of embryogenesis. Inhibition of Wnt signaling is beneficial for cardiac wound healing and functional recovery after injury. Understanding of the roles and mechanisms of Wnt signaling pathway in injured animal hearts will contribute to the development of potential therapeutics for human diseased hearts.
目的综述：心血管疾病是全球范围内主要的致死病因，这主要是由于成年人心脏的再生能力有限。相比之下，硬骨鱼斑马鱼的心脏在受伤后可通过已有心肌细胞的增殖实现自然再生。如果在出生后几天内对小鼠的心脏造成损伤，其也具有再生能力，这与心肌细胞增殖的短暂能力一致。本文主要综述了 Wnt/β-连环蛋白信号通路在哺乳动物和非哺乳动物脊椎动物心脏发育和再生中的作用和机制。
最新发现：在斑马鱼、小鼠和人类胚胎干细胞中的研究表明，Wnt/β-连环蛋白信号在心脏发育过程中具有双重作用。在心脏发育和损伤修复过程中，多种细胞类型均会诱导产生 Wnt 和 Wnt 拮抗剂。在本文中，我们总结了 Wnt 信号通路的组成及其不同作用途径，随后讨论了它们在心脏特化、增殖和模式形成中的作用。我们概述了 Wnt/β-连环蛋白信号在心脏稳态、重塑和再生过程中的经典和非经典活性。Wnt 信号的抑制对心脏伤口愈合和损伤后功能恢复有益。了解 Wnt 信号通路在受伤动物心脏中的作用和机制，将有助于开发针对人类患病心脏的潜在治疗方法。
