Song Yonghuan, Ding Jian, Jin Rilong, Jung Jinhee, Li Shi, Yang Jingquan, Wang Anyuan, Li Zhijie
Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
Department of Orthopedic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
Mol Med Rep. 2016 Apr;13(4):3619-26. doi: 10.3892/mmr.2016.4942. Epub 2016 Feb 26.
Fibroblast growth factor (FGF)21 functions in the maintenance of glucose homeostasis and exerts protective effects on the liver, heat and kidneys. However, the roles of FGF21 in other tissue types are yet to be fully elucidated. The present study detected elevated expression levels of FGF21 in skin tissue. Furthermore, it was revealed that FGF21 expression in the skin was induced upon wounding. In addition, β‑klotho expression was detected in the skin tissue. To examine the role of FGF21 in the wound healing process, recombinant human (h)FGF21 was expressed in a the yeast strain Pichia (P.) pastoris, a well‑known system for recombinant protein production. Based on the sequence of hFGF21 and the optimal codon of P. pastoris, codon‑optimized FGF21 open reading frame sequences were obtained using seven pairs of 55‑59‑nt primers with seven rounds of PCR. The recombinant FGF21 was purified and its function was examined in human fibroblast cells using a wound healing cell migration assay. Treatment with FGF21 promoted cell migration, which is an important step in wound healing. Furthermore, FGF21 treatment enhanced the activity of c‑Jun N‑terminal kinase, a key regulator in fibroblast‑cell migration. In conclusion, FGF21 is induced after wounding and FGF21 expressed and purified from yeast markedly accelerates wound healing. The present study was the first to elucidate the function of FGF21 in skin tissues and provided a theoretical basis for the use of FGF21 in the treatment of skin wounds.
成纤维细胞生长因子（FGF）21在维持葡萄糖稳态中发挥作用，并对肝脏、心脏和肾脏具有保护作用。然而，FGF21在其他组织类型中的作用尚未完全阐明。本研究检测到皮肤组织中FGF21的表达水平升高。此外，研究发现皮肤中的FGF21表达在受伤后被诱导。此外，在皮肤组织中检测到β-klotho的表达。为了研究FGF21在伤口愈合过程中的作用，重组人（h）FGF21在酵母菌株巴斯德毕赤酵母（P. pastoris）中表达，这是一种众所周知的重组蛋白生产系统。基于hFGF21的序列和巴斯德毕赤酵母的最佳密码子，使用七对55-59个核苷酸的引物通过七轮PCR获得密码子优化的FGF21开放阅读框序列。重组FGF21被纯化，并使用伤口愈合细胞迁移试验在人成纤维细胞中检测其功能。用FGF21处理促进了细胞迁移，这是伤口愈合中的一个重要步骤。此外，FGF21处理增强了c-Jun N末端激酶的活性，该激酶是成纤维细胞迁移的关键调节因子。总之，FGF21在受伤后被诱导，从酵母中表达和纯化的FGF21显著加速伤口愈合。本研究首次阐明了FGF21在皮肤组织中的功能，并为FGF21用于治疗皮肤伤口提供了理论依据。
