Yokoyama Hitoshi, Kudo Nanako, Todate Momoko, Shimada Yuri, Suzuki Makoto, Tamura Koji
Department of Biochemistry and Molecular Biology, Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Aomori, Japan.
Division of Morphogenesis, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Aichi, Japan.
Dev Growth Differ. 2018 Aug;60(6):316-325. doi: 10.1111/dgd.12544. Epub 2018 Jun 26.
Adult mammals do not regenerate the dermis of the skin but form a scar after a deep skin injury. Since a scar causes serious medical problems, skin regeneration, instead of formation of a scar, has been strongly desired from a clinical point of view. Recent studies have suggested multiple origins of myofibroblasts, which are scar-forming cells in skin wound healing of mammals. While amphibians have skin structures that are basically common to mammals as tetrapods, both urodele and anuran amphibians regenerate almost complete skin structures including the dermis and secretion glands without forming a remarkable scar after a deep skin injury. In skin regeneration of a metamorphosed Xenopus laevis, an amphibian, cells that resemble limb blastema cells accumulate under the epidermis after injury and cells from subcutaneous tissues (tissues underlying the skin) contribute to skin regeneration. The skin of urodele amphibians and that of anuran amphibians provide valuable models for studying skin regeneration as adults. Recent progress in transgenesis and genome editing techniques with whole genome sequencing in Xenopus and an axolotl have enabled comparative analyses by molecular genetics of mammal skin and amphibian skin. Such comparative analyses would enable direct comparison of scar-forming myofibroblasts in mammals and blastema-like cells that contribute to skin regeneration in amphibians, ultimately leading to realization of skin regeneration in adult mammals. Amphibian skin regeneration will also be useful for determining how to step up skin regeneration to a higher level of regeneration such as limb regeneration in the future.
成年哺乳动物不会再生皮肤的真皮层，而是在深度皮肤损伤后形成瘢痕。由于瘢痕会引发严重的医学问题，从临床角度来看，人们一直强烈期望实现皮肤再生而非形成瘢痕。最近的研究表明，成纤维细胞有多种来源，而成纤维细胞是哺乳动物皮肤伤口愈合过程中形成瘢痕的细胞。两栖动物作为四足动物，其皮肤结构与哺乳动物基本相同，有尾目和无尾目两栖动物在深度皮肤损伤后都能再生几乎完整的皮肤结构，包括真皮层和分泌腺，且不会形成明显的瘢痕。在变态后的非洲爪蟾（一种两栖动物）的皮肤再生过程中，受伤后类似肢体芽基细胞的细胞会在表皮下聚集，皮下组织（皮肤下方的组织）中的细胞也会参与皮肤再生。有尾目两栖动物和无尾目两栖动物的皮肤为研究成年动物的皮肤再生提供了有价值的模型。非洲爪蟾和蝾螈的转基因和基因组编辑技术以及全基因组测序的最新进展，使得能够通过分子遗传学对哺乳动物皮肤和两栖动物皮肤进行比较分析。这种比较分析将能够直接比较哺乳动物中形成瘢痕的成纤维细胞和两栖动物中参与皮肤再生的类芽基细胞，最终实现成年哺乳动物的皮肤再生。两栖动物的皮肤再生对于确定如何将皮肤再生提升到更高水平的再生（如未来的肢体再生）也将很有用。
