Shi De-Li
Department of Medical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
Laboratory of Developmental Biology (CNRS-UMR7622), Institute de Biologie Paris-Seine (IBPS), Sorbonne University, 75005 Paris, France.
Int J Mol Sci. 2023 Jul 26;24(15):12004. doi: 10.3390/ijms241512004.
Myocardial injury causes death to cardiomyocytes and leads to heart failure. The adult mammalian heart has very limited regenerative capacity. However, the heart from early postnatal mammals and from adult lower vertebrates can fully regenerate after apical resection or myocardial infarction. Thus, it is of particular interest to decipher the mechanism underlying cardiac regeneration that preserves heart structure and function. RNA-binding proteins, as key regulators of post-transcriptional gene expression to coordinate cell differentiation and maintain tissue homeostasis, display dynamic expression in fetal and adult hearts. Accumulating evidence has demonstrated their importance for the survival and proliferation of cardiomyocytes following neonatal and postnatal cardiac injury. Functional studies suggest that RNA-binding proteins relay damage-stimulated cell extrinsic or intrinsic signals to regulate heart regenerative capacity by reprogramming multiple molecular and cellular processes, such as global protein synthesis, metabolic changes, hypertrophic growth, and cellular plasticity. Since manipulating the activity of RNA-binding proteins can improve the formation of new cardiomyocytes and extend the window of the cardiac regenerative capacity in mammals, they are potential targets of therapeutic interventions for cardiovascular disease. This review discusses our evolving understanding of RNA-binding proteins in regulating cardiac repair and regeneration, with the aim to identify important open questions that merit further investigations.
心肌损伤会导致心肌细胞死亡并引发心力衰竭。成年哺乳动物的心脏再生能力非常有限。然而，出生后早期哺乳动物以及成年低等脊椎动物的心脏在进行心尖切除或心肌梗死后能够完全再生。因此，破译维持心脏结构和功能的心脏再生潜在机制具有特别重要的意义。RNA结合蛋白作为转录后基因表达的关键调节因子，可协调细胞分化并维持组织内稳态，在胎儿和成年心脏中呈现动态表达。越来越多的证据表明，它们对于新生儿和出生后心脏损伤后心肌细胞的存活和增殖至关重要。功能研究表明，RNA结合蛋白传递损伤刺激的细胞外或细胞内信号，通过重新编程多个分子和细胞过程来调节心脏再生能力，如整体蛋白质合成、代谢变化、肥大生长和细胞可塑性。由于操纵RNA结合蛋白的活性可以促进新心肌细胞的形成并延长哺乳动物心脏再生能力的窗口期，因此它们是心血管疾病治疗干预的潜在靶点。本综述讨论了我们对RNA结合蛋白在调节心脏修复和再生方面不断发展的认识，旨在确定值得进一步研究的重要开放性问题。
