Um JungIn, Jung Da-Woon, Williams Darren Reece
New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju, 61005, Republic of Korea.
Clin Transl Med. 2017 Dec;6(1):13. doi: 10.1186/s40169-017-0143-8. Epub 2017 Mar 22.
The ability of salamanders, such as newts, to regenerate damaged tissues has been studied for centuries. A prominent example of this regenerative power is the ability to re-grow entire amputated limbs. One important step in this regeneration process is skeletal muscle cellularization, in which the muscle fibers break down into dedifferentiated, mononuclear cells that proliferate and form new muscle in the replacement limb. In contrast, mammalian skeletal muscle does not undergo cellularization after injury. A significant proportion of research about tissue regeneration in salamanders aims to characterize regulatory genes that may have mammalian homologs. A less mainstream approach is to develop small molecule compounds that induce regeneration-related mechanisms in mammals. In this commentary, we discuss progress in discovering small molecules that induce cellularization in mammalian muscle. New research findings using these compounds has also shed light on cellular processes that regulate cellularization, such as apoptotic signaling. Although formidable technical hurdles remain, this progress increases our understanding of tissue regeneration and provide opportunities for developing small molecules that may enhance tissue repair in humans.
几个世纪以来，蝾螈等蝾螈科动物再生受损组织的能力一直是研究的对象。这种再生能力的一个突出例子是能够重新长出整个被截断的肢体。这个再生过程中的一个重要步骤是骨骼肌细胞化，即肌纤维分解成去分化的单核细胞，这些细胞增殖并在替换肢体中形成新的肌肉。相比之下，哺乳动物的骨骼肌在受伤后不会发生细胞化。关于蝾螈组织再生的大量研究旨在鉴定可能具有哺乳动物同源物的调控基因。一种不太主流的方法是开发能在哺乳动物中诱导再生相关机制的小分子化合物。在这篇评论中，我们讨论了在发现能诱导哺乳动物肌肉细胞化的小分子方面取得的进展。使用这些化合物的新研究结果也揭示了调节细胞化的细胞过程，如凋亡信号传导。尽管仍然存在巨大的技术障碍，但这一进展增进了我们对组织再生的理解，并为开发可能增强人类组织修复的小分子提供了机会。
