The initiation of the wound healing program is regulated by the convergence of mechanical and epigenetic cues

Abstract

Wound healing in the skin is a complex physiological process that is a product of a cell state transition from homeostasis to repair. Mechanical cues are increasingly being recognized as important regulators of cellular reprogramming, but the mechanism by which it is translated to changes in gene expression and ultimately cellular behavior remains largely a mystery. To probe the molecular underpinnings of this phenomenon further, we used the downregulation of caspase-8 as a biomarker of a cell entering the wound-healing program. We found that the wound-induced release of tension within the epidermis leads to the alteration of gene expression via the nuclear translocation of the DNA methyltransferase 3A (DNMT3a). This enzyme then methylates promoters of genes that are known to be downregulated in response to wound stimuli as well as potentially novel players in the repair program. Overall, these findings illuminate the convergence of mechanical and epigenetic signaling modules that are important regulators of the transcriptome landscape required to initiate the tissue repair process in the differentiated layers of the epidermis.

Modulation of gene expression in skin wound healing by photobiomodulation therapy: A systematic review in vivo studies

“…In addition to its role in normal development, DNMT3A positively regulates the expression of genes involved in stem cell proliferation and promotes the expression of genes that drive epidermal differentiation 46 . Bhatt et al 47 . demonstrated that after skin injury, cells near the wound edge expressed DNMT3A.…”

Mindin differentially regulates fibroblast subpopulations via distinct members of the Src family kinases during fibrogenesis

“…All cells were maintained, and experiments were performed until passage # 5. Mouse epidermal keratinocytes were harvested from P2/P3 epidermis and were cultured in low calcium E-media to maintain undifferentiated proliferating state as previously described 57 .…”