Khajornpipat Patcharin, Reamtong Onrapak, Aunpad Ratchaneewan
Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, Thailand.
Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
PLoS One. 2025 May 14;20(5):e0323363. doi: 10.1371/journal.pone.0323363. eCollection 2025.
Treatment of chronic or non-healing wounds has faced a considerable clinical challenge and impose several detrimental effects on individuals, society, the healthcare system, and the economy. Bioactive peptides have been employed to accelerate wound healing in active wound treatment efficiently and effectively. In the current study, a novel wound-healing peptide, WHP1, was designed from 23 existing wound-healing peptides by a rational template-assisted approach. It demonstrated the ability to enhance migration and proliferation of human keratinocyte cell lines (HaCaT) without exhibiting cytotoxic effects on human red blood cells and HaCaT cells. By quantitative proteomic analysis, WHP1 exerted a multifaceted role on diverse cellular processes in human keratinocyte. Notably, it increased the expression of intracellular proteins of HaCaT cells involved in cell cycle regulation and focal adhesion, including centromeric histone H3 variant CENPA, ubiquitin-conjugating enzyme E2 C, thyroid receptor-interacting protein 6, and ribosomal components essential for cell adhesion and migration. WHP1 upregulated the key enzyme glyceraldehyde-3-phosphate dehydrogenase, orchestrating metabolic biosynthesis particularly glycolysis, cell cycle regulation, and cytoskeletal processes. An intriguing observation was the antioxidant activity of WHP1, protecting cells from reactive oxygen species-induced senescence. This is consistent with the upregulation of GAPDH expression and reduction of histone H2A.J levels. WHP1 also stimulated macrophages to secrete transforming growth factor-β (TGF-β), a crucial growth factor necessary for the remodeling phase of wound healing. This investigation highlighted the feasibility of rational design to create novel wound-healing peptides. Such advancements hold promise for improving patients' quality of life and elevating the standard of care in contemporary healthcare.
慢性伤口或难愈合伤口的治疗面临着巨大的临床挑战，并对个人、社会、医疗保健系统和经济造成了若干不利影响。生物活性肽已被用于在积极的伤口治疗中有效且高效地加速伤口愈合。在本研究中，通过合理的模板辅助方法，从23种现有的伤口愈合肽中设计出了一种新型伤口愈合肽WHP1。它显示出增强人角质形成细胞系（HaCaT）迁移和增殖的能力，且对人红细胞和HaCaT细胞无细胞毒性作用。通过定量蛋白质组学分析，WHP1在人角质形成细胞的多种细胞过程中发挥了多方面作用。值得注意的是，它增加了HaCaT细胞中参与细胞周期调控和粘着斑的细胞内蛋白质的表达，包括着丝粒组蛋白H3变体CENPA、泛素结合酶E2 C、甲状腺受体相互作用蛋白6以及细胞粘附和迁移所必需的核糖体成分。WHP1上调了关键酶甘油醛-3-磷酸脱氢酶，协调代谢生物合成，特别是糖酵解、细胞周期调控和细胞骨架过程。一个有趣的发现是WHP1的抗氧化活性，可保护细胞免受活性氧诱导的衰老。这与GAPDH表达的上调和组蛋白H2A.J水平的降低一致。WHP1还刺激巨噬细胞分泌转化生长因子-β（TGF-β），这是伤口愈合重塑阶段所需的一种关键生长因子。本研究突出了合理设计以创造新型伤口愈合肽的可行性。这些进展有望改善患者的生活质量并提升当代医疗保健的护理标准。
