Epigenetic remodeling of M2 macrophage polarization in skin wound healing: Mechanisms and therapeutic implications

Wound healing is a complex and tightly regulated process involving stages such as inflammation, anti-inflammation, regeneration, and resolution. Macrophages, known for their plasticity, play a crucial role in regulating these processes. In response to cytokine signals in the microenvironment, macrophages polarize into M1 or M2 subtypes, each with distinct gene expression profiles and functions. M2 macrophages are particularly important for anti-inflammation, antiparasitic infection, and tissue repair, with their activities closely related to epigenetic regulation. This review synthesizes evidence on the epigenetic mechanisms—including histone modifications, DNA methylation, and non-coding RNA networks—governing M2 polarization in both acute and chronic wound healing contexts, and highlights the application of epigenetic regulatory strategies to modulate their biological functions. These insights not only elucidate the molecular underpinnings of wound repair but also offer potential pathways for developing epigenetic-based therapeutic interventions to enhance healing, particularly in chronic wounds.