Department of Biochemistry and Medical Chemistry, University of Pecs, Medical School, Pecs H-7624, Hungary; Szentagothai Research Centre, Research Group of Regenerative Science, Sport and Medicine, University of Pecs, Pecs H-7624, Hungary.
Department of Biochemistry and Medical Chemistry, University of Pecs, Medical School, Pecs H-7624, Hungary; Szentagothai Research Centre, Research Group of Regenerative Science, Sport and Medicine, University of Pecs, Pecs H-7624, Hungary.
Int Immunopharmacol. 2023 Mar;116:109741. doi: 10.1016/j.intimp.2023.109741. Epub 2023 Jan 27.
Our dream of defeating the processes of organ damage and aging remains a challenge scientists pursued for hundreds of years. Although the goal is to successfully treat the body as a whole, steps towards regenerating individual organs are even considered significant. Since initial approaches utilizing only progenitor cells appear limited, we propose interconnecting our collective knowledge regarding aging and embryonic development may lead to the discovery of molecules which provide alternatives to effectively reverse cellular damage. In this review, we introduce and summarize our results regarding Thymosin beta-4 (TB4) to support our hypothesis using the heart as model system. Accordingly, we investigated the developmental expression of TB4 in mouse embryos and determined the impact of the molecule in adult animals by systemically injecting the peptide following acute cardiac infarction or with no injury. Our results proved, TB4 is expressed in the developing heart and promotes cardiac cell migration and survival. In adults, the peptide enhances myocyte survival and improves cardiac function after coronary artery ligation. Moreover, intravenous injections of TB4 alter the morphology of the adult epicardium, and the changes resemble the characteristics of the embryo. Reactivation of the embryonic program became equally reflected by the increased number of cardiac vessels and by the alteration of the gene expression profile typical of the embryonic state. Moreover, we discovered TB4 is capable of epicardial progenitor activation, and revealed the effect is independent of hypoxic injury. By observing the above results, we believe, further discoveries and consequential postnatal administration of developmentally relevant candidate molecules such as TB4 may likely result in reversing aging processes and accelerate organ regeneration in the human body.
我们将器官损伤和衰老过程击败的梦想仍然是一个挑战，数百年来，科学家们一直在追求这个目标。虽然目标是成功地将身体作为一个整体进行治疗，但朝着再生单个器官的步骤甚至被认为是重要的。由于最初仅利用祖细胞的方法似乎有限，我们提出，将我们关于衰老和胚胎发育的集体知识相互关联，可能会发现提供有效逆转细胞损伤替代方案的分子。在这篇综述中，我们介绍并总结了我们关于胸腺素β-4（TB4）的结果，以支持我们使用心脏作为模型系统的假设。因此，我们研究了 TB4 在小鼠胚胎中的发育表达，并通过在急性心肌梗塞后或无损伤时系统注射该肽，确定了该分子对成年动物的影响。我们的结果证明，TB4 在发育中的心脏中表达，并促进心脏细胞的迁移和存活。在成年动物中，该肽可增强心肌细胞的存活并改善冠状动脉结扎后的心脏功能。此外，TB4 的静脉内注射可改变成年心外膜的形态，并且变化类似于胚胎的特征。胚胎程序的重新激活同样反映在心脏血管数量的增加以及胚胎状态典型的基因表达谱的改变上。此外，我们发现 TB4 能够激活心外膜祖细胞，并揭示该作用独立于缺氧损伤。通过观察上述结果，我们相信，进一步的发现和随后对 TB4 等与发育相关的候选分子的产后给药，可能会导致逆转衰老过程并加速人体器官再生。
