Zhu Lijun, Huang Wenjie, Shi Jingjing, Li Fei, Sun Xiuxia, Xiao Jianxi
School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou 730000, PR China.
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China; Gansu Engineering Research Center of Medical Collagen, Lanzhou 730000, PR China.
Int J Biol Macromol. 2025 Aug;319(Pt 4):145467. doi: 10.1016/j.ijbiomac.2025.145467. Epub 2025 Jun 24.
The degradation of elastin in aged skin results in the loss of elasticity, the formation of wrinkles, and even a reduced ability for wound healing after injury. However, previous studies about elastin material have been limited by high immunogenicity of animal-derived elastin, the use of single elastin peptide sequences, and residual crosslinking agents. In this study, we designed a multipotent anti-aging recombinant human elastin (rElastin) and utilized it to counteract caudal fin shrinkage in zebrafish and D-galactose-induced intrinsic skin aging in mice. The rElastin demonstrated thermoresponsive reversible phase-transition closely resembling that of natural elastin. In vitro, cell experiments demonstrated that rElastin effectively promoted the proliferation, adhesion, and spreading of HFF-1 cells. In a D-galactose-induced intrinsic aging mouse model, rElastin significantly restored dermal density, skin hydration, and TEWL to levels approaching those of healthy skin. Histological analysis further confirmed that rElastin facilitated the deposition of collagen and regeneration of elastic fibers, thereby promoting structural and functional repair of aging skin. Additionally, rElastin obviously inhibited the tail fin shrinkage after UV radiation. rElastin effectively targets skin symptoms associated with intrinsic aging, providing fresh insights into anti-aging therapies and showcasing strong potential for applications in regenerative medicine and cosmetic dermatology.
衰老皮肤中弹性蛋白的降解会导致弹性丧失、皱纹形成，甚至受伤后伤口愈合能力下降。然而，以往关于弹性蛋白材料的研究受到动物源性弹性蛋白免疫原性高、单一弹性蛋白肽序列的使用以及残留交联剂的限制。在本研究中，我们设计了一种多能抗衰重组人弹性蛋白（rElastin），并利用它来对抗斑马鱼的尾鳍收缩和D-半乳糖诱导的小鼠皮肤内源性衰老。rElastin表现出与天然弹性蛋白极为相似的热响应可逆相变。在体外，细胞实验表明rElastin能有效促进人包皮成纤维细胞（HFF-1）的增殖、黏附和铺展。在D-半乳糖诱导的内源性衰老小鼠模型中，rElastin显著将皮肤密度、皮肤水合作用和经皮水分流失恢复至接近健康皮肤的水平。组织学分析进一步证实，rElastin促进了胶原蛋白的沉积和弹性纤维的再生，从而促进了衰老皮肤的结构和功能修复。此外，rElastin明显抑制了紫外线辐射后的尾鳍收缩。rElastin有效针对与内源性衰老相关的皮肤症状，为抗衰疗法提供了新见解，并在再生医学和美容皮肤科领域展现出强大的应用潜力。
