Keloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.

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瘢痕疙瘩的表观遗传修饰机制：现状与展望

瘢痕疙瘩是一种常见的皮肤纤维增生性疾病，是一种以成纤维细胞侵袭性增殖和细胞外基质过度积累为特征的良性皮肤肿瘤。然而，瘢痕疙瘩的常见治疗方法效果有限，强调开发创新机制和治疗策略的重要性。表观遗传学代表遗传学和外部风险因素之间复杂相互作用的潜在联系，目前正受到严格​​审查。越来越多的证据表明，以 DNA 甲基化、组蛋白修饰和非编码 RNA (ncRNA) 为代表的多种多样和可逆的表观遗传修饰在瘢痕疙瘩的基因调控和下游成纤维细胞功能中发挥着关键作用。重要的，异常表观遗传修饰操纵瘢痕疙瘩衍生的成纤维细胞的多种行为，瘢痕疙瘩皮肤组织中的主要细胞成分包括增殖、迁移、凋亡和分化。在这里，我们回顾和总结了目前可用的临床和实验研究，以深入研究瘢痕疙瘩进展中的表达谱并阐明表观遗传修饰的机制，主要包括 DNA 甲基化、组蛋白修饰和 ncRNA（miRNA、lncRNA 和 circRNA ）。此外，我们还提供了与瘢痕疙瘩表观遗传学修饰相关的挑战和未来前景。破译瘢痕疙瘩中复杂的表观遗传修饰有望为瘢痕疙瘩的发病机制和诊断/治疗靶点带来新的见解，