Tripeptides containing lysine such as Arg-His-Lys (AHK) and Gly-His-Lys (GHK) are known to modulate biological regeneration. Here, we synthesized and evaluated the biological effects of dimeric peptide derivatives on the proliferation of human follicle dermal papilla cells (HFDPCs) in an in vitro model. Treatment of dimeric peptide derivatives stimulated the proliferation of HFDPCs more when compared to the group treated with AHK. Dimeric peptide derivatives also stimulated the phosphorylation of mitogen-activated protein kinases extracellular signal-regulated kinase (ERK1/2). In particular, peptide No. 20 Arg-Trp-Lys (AWK') was found to promote the phosphorylation of ERK1/2 most strongly. In addition, peptide No. 20 (AWK') activated mRNA expression of hair regeneration-related genes such as VEGF, FGF-2, and FGF-7. Our results suggest that dimeric peptide derivatives exert a stimulating effect on HFDPC proliferation through activation of ERK1/2 signaling and without significant cytotoxicity. These results provide important data for the development of peptide-based hair-regenerative agents and treatment of alopecia.

中文翻译：

---

作为人卵泡真皮乳头细胞增殖刺激剂的二聚肽衍生物的合成和生物学评价

已知含有赖氨酸的三肽如 Arg-His-Lys (AHK) 和 Gly-His-Lys (GHK) 可调节生物再生。在这里，我们在体外模型中合成并评估了二聚肽衍生物对人卵泡真皮乳头细胞 (HFDPC) 增殖的生物学影响。与用 AHK 处理的组相比，二聚肽衍生物的处理更能刺激 HFDPC 的增殖。二聚肽衍生物还刺激丝裂原活化蛋白激酶胞外信号调节激酶 (ERK1/2) 的磷酸化。特别是，发现第 20 号肽 Arg-Trp-Lys (AWK') 最强烈地促进 ERK1/2 的磷酸化。此外，20号肽（AWK'）激活毛发再生相关基因如VEGF的mRNA表达、FGF-2和FGF-7。我们的结果表明，二聚肽衍生物通过激活 ERK1/2 信号传导对 HFDPC 增殖产生刺激作用，并且没有显着的细胞毒性。这些结果为开发基于肽的毛发再生剂和治疗脱发提供了重要数据。