Causes and consequences of epigenetic regulation in wound healing.

Wound healing is a complex and systematic tissue level response to mechanical and chemical injuries that may cause the release of growth factors, cytokines, and chemokines by damaged tissues. For the complex features of these restorative processes, it is a crucial challenge to identify the relevant cell types and biochemical pathways that are involved in wound healing. Epigenetic mechanisms, such as DNA methylation, histone modification, and noncoding regulatory RNA editing, play important roles in many biological processes, including cell proliferation, migration and differentiation, signal pathway activation or inhibition, and cell senescence. Epigenetic regulations can coordinately control a considerable subset of known repair genes and thus serve as master regulators of wound healing. An abundance of evidence has also shown that epigenetic modifications participate in the short- and long-term control of crucial gene expression and cell signal transduction that are involved in the healing process. These data provide a foundation for probable epigenetic-based therapeutic strategies that are aimed at stimulating tissue regeneration. This review describes the epigenetic alterations in different cellular types at injury sites, induced signals, and resulting tissue repair. With the increased interest in the epigenetics of wound and repair processes, this field will soon begin to flourish.