创面高糖环境干预角质细胞增殖和迁移的机制及其靶向治疗的新进展

Mechanisms of high-glucose environment-induced impairment of keratinocyte proliferation and migration in wounds: recent advances in targeted therapies

摘要:

阐明高糖环境干预角质细胞功能的核心机制，并评述以其为靶点的治疗策略，为糖尿病创面治疗提供理论依据。系统梳理高糖环境通过信号通路异常、自噬失衡及表观遗传重编程介导角质细胞功能障碍的分子网络，并分类总结相关外用治疗策略的作用机制。高糖通过干扰ERK1/2-PI3K/Akt等通路、抑制自噬、引发基质金属蛋白酶9启动子脱甲基化及非编码RNA失调，导致生长因子网络失衡，阻碍角质细胞增殖和迁移。血小板衍生生长因子-BB、干细胞外泌体等多种活性物质通过补充关键分子或调控信号网络展现出治疗潜力。中医药复方呈现多靶点干预优势。糖尿病创面愈合障碍涉及多层级网络失调，未来治疗需转向多靶点调控，并借助系统生物学与新型递送技术推动临床转化。

Abstract:

This review aims to elucidate the core mechanisms by which a high-glucose environment impairs keratinocyte function and to summarize related targeted therapeutic strategies, thereby providing a theoretical basis for diabetic wound treatment. We synthesized the molecular networks through which high glucose mediates keratinocyte dysfunction via aberrant signaling pathways, autophagy imbalance, and epigenetic reprogramming. The mechanisms of action of various topical therapeutic strategies were categorized and summarized. High glucose disrupts the proliferation and migration of keratinocytes by interfering with pathways such as ERK1/2 and PI3K/Akt, inhibiting autophagy, and inducing epigenetic alterations including matrix metalloproteinase-9 (MMP-9) promoter demethylation and non-coding RNA dysregulation, ultimately leading to an imbalance in the growth factor network. Multiple bioactive substances, such as platelet-derived growth factor-BB (PDGF-BB) and stem cell-derived exosomes, demonstrate therapeutic potential by supplementing key molecules or modulating signaling networks. Traditional Chinese Medicine compounds exhibit advantages through multi-target interventions. Impairment of diabetic wound healing involves dysregulation of multi-level networks. Future therapies should focus on multi-target regulation and utilize systems biology and novel delivery technologies to facilitate clinical translation.