Effects of the led therapy on the global DNA methylation and the expression of Dnmt1 and Dnmt3a genes in a rat model of skin wound healing

Abstract

The use of light emitting diodes (LED) as a therapeutic resource for wound healing has increased over the last years; however, little is still known about the molecular pathways associated to LED exposure. In the present study, we verified the effects of LED therapy on DNA methylation and expression of the DNA methyltransferase (Dnmt) genes, Dnmt1 and Dnmt3a, in an in vivo model of epithelial wound healing. Male Wistar rats were submitted to epithelial excision in the dorsal region and subsequently distributed within the experimental groups: group 1, animals that received irradiation of 0.8 J/cm(2) of LED (604 nm); group 2, animals that received 1.6 J/cm(2) of LED (604 nm); control (CTL), animals not submitted to therapeutic intervention. LED applications were performed during 7 days, and tissues from the periphery of the wound area were obtained for molecular analysis. The Image-J software was used for analysis of the wound area. DNA methylation was evaluated by ELISA-based method and gene expressions were quantified by real-time PCR. Decrease on global DNA methylation profile was observed in all experimental groups (CTL, 1, and 2) revealing the participation of DNA methylation in the healing process. Significant decrease in the wound area accompanied by increase in the Dnmt3a expression was associated to group 2. Based on our findings, we propose that DNA methylation is an important molecular mechanism associated to wound healing and that irradiation with 1.6 J/cm(2) of LED evokes an increase in the expression of the Dnmt3a that might associates to the efficiency of the epithelial wound healing.

JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing

“…However, very few reports demonstrated that DNA methylation is implicated on skin wound healing. For example, decreased level of global DNA methylation is observed in rat skin wound healing 21 . In contrast to DNA methylation, several reports demonstrated the importance of histone modification or histone-modifying enzymes in skin wound healing.…”

DNMT1-mediated methylation inhibits microRNA-214-3p and promotes hair follicle stem cell differentiate into adipogenic lineages

“…DNA methylation has been elucidated as a critical molecular mechanism to be of importance to the skin wound healing process and nociceptive sensitization following skin incision [2,26]. Additionally, DNMTs are known to participate in the self-renewal and senescence of human HFSc, which are recognized to be recruited to the skin injury site for further differentiation to repair injured epithelium [27].…”

“…In the early stage of skin trauma, the basal cells at the edge of the wound begin to proliferate and form a single layer of epithelium, which covers the surface of the granulation tissues of the wound and then differentiate into squamous epithelium [1,2]. Differentiation of epithelial cells is the key process of epidermal wound repair.…”

DNA Methylation Regulates Corneal Epithelial Wound Healing by Targeting miR-200a and CDKN2B

“…Our findings may also provide valuable information for wound healing that occurs in other tissues, such as skin, as there may be similar shared mechanisms. 38,39 Although the DNA methylation levels vary in different tissues, the DNA methylation status of specific gene promoters in different individuals is the same. 40 Increasing evidence suggests that epigenetic silencing of miRNA gene expression by CpG hypermethylation is also emerging as a common hallmark of physiological development and specific diseases.…”