Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Road, Jiaushi, Ilan 262, Taiwan.
Mar Drugs. 2022 Mar 10;20(3):205. doi: 10.3390/md20030205.
Wound healing is a highly orchestrated process involving many cell types, such as keratinocytes, fibroblasts and endothelial cells. This study aimed to evaluate the potential application of synthetic peptides derived from tilapia piscidin (TP)2, TP2-5 and TP2-6 in skin wound healing. The treatment of HaCaT keratinocytes with TP2-5 and TP2-6 did not cause cytotoxicity, but did enhance cell proliferation and migration, which could be attributed to the activation of epidermal growth factor receptor signaling. In CCD-966SK fibroblasts, although TP2-5 (31.25 μg/mL) and TP2-6 (125 μg/mL) showed cytotoxic effects, we observed the significant promotion of cell proliferation and migration at low concentrations. In addition, collagen I, collagen III, and keratinocyte growth factor were upregulated by the peptides. We further found that TP2-5 and TP2-6 showed pro-angiogenic properties, including the enhancement of human umbilical vein endothelial cell (HUVEC) migration and the promotion of neovascularization. In a murine model, wounds treated topically with TP2-5 and TP2-6 were reduced by day 2 post-injury and healed significantly faster than untreated wounds. Taken together, these findings demonstrate that both TP2-5 and TP2-6 have multifaceted effects when used as topical agents for accelerating wound healing.
伤口愈合是一个高度协调的过程，涉及许多细胞类型，如角质形成细胞、成纤维细胞和内皮细胞。本研究旨在评估从罗非鱼抗菌肽（TP）2、TP2-5 和 TP2-6 衍生的合成肽在皮肤伤口愈合中的潜在应用。TP2-5 和 TP2-6 处理 HaCaT 角质形成细胞不会引起细胞毒性，但确实增强了细胞增殖和迁移，这可能归因于表皮生长因子受体信号的激活。在 CCD-966SK 成纤维细胞中，虽然 TP2-5（31.25μg/ml）和 TP2-6（125μg/ml）表现出细胞毒性作用，但我们在低浓度下观察到细胞增殖和迁移的显著促进。此外，肽上调了胶原蛋白 I、胶原蛋白 III 和角质形成细胞生长因子。我们进一步发现，TP2-5 和 TP2-6 具有促血管生成特性，包括增强人脐静脉内皮细胞（HUVEC）迁移和促进新血管形成。在小鼠模型中，经皮局部应用 TP2-5 和 TP2-6 可在损伤后第 2 天减少伤口，并显著加快未治疗伤口的愈合速度。综上所述，这些发现表明，TP2-5 和 TP2-6 作为加速伤口愈合的局部制剂具有多方面的作用。
