Epigenetic regulation of cellular functions in wound healing

Abstract

Cutaneous wound healing is a complex process involving numerous cell types to accomplish sequential, yet overlapping phases of inflammation, proliferation and tissue remodelling. 1,2 Immediately after injury, blood components are released into the wound, forming a clot which provides a matrix for the influx of inflammatory cells.The inflammatory phase is characterized by leukocyte migration to the wound. Neutrophils primarily remove bacteria, followed by monocytes which further differentiate into macrophages that exert early pro-inflammatory and late anti-inflammatory functions during the healing process. Deposition of the newly synthesized fibrin matrix and granulation tissue formation follow; these are subsequently replaced by collagen and scar tissue during the final stages of wound healing. The proliferative phase of wound healing is characterized by re-epithelialization, neovascularization and extracellular matrix deposition. 1,3 Historically, exploration of the molecular basis of wound healing has included a primary focus on its spatiotemporal regulation. Given the complexity of the wound healing process and its requirement for stringent regulation, epigenetic regulation including histone modifications and DNA methylation is highly likely to play a role. 4,5 Indeed, recent discoveries in the field of non-coding RNAs have identified roles for microRNAs (miRs), circular RNAs (circRNA) and long noncoding RNAs (lncRNA) as global gene expression regulators involved in an array of processes important for successful wound healing. [6][7][8][9] While the primary focus of previous reviews has been on the role of epigenetic modifications in acute wound healing, 4-8 herein we

Cellular reprogramming of diabetic foot ulcer fibroblasts triggers pro‐healing miRNA‐mediated epigenetic signature

“…Understanding the role of miR in somatic reprogramming of healing-impaired fibroblasts is of particular significance, as miRs are recognized major regulators of cellular processes that contribute to wound healing and its impairment. 2,15,29,43 In addition, miRs can promote pluripotent reprogramming and may even offer an approach to substitute for the pluripotency transcription factors. 15 As the efficiency of iPSC reprogramming continues to increase, this autologous cell-based therapeutic approach could make its way to clinical application for chronic non-healing DFU.…”

“…2,15,29,43 In addition, miRs can promote pluripotent reprogramming and may even offer an approach to substitute for the pluripotency transcription factors. 15 As the efficiency of iPSC reprogramming continues to increase, this autologous cell-based therapeutic approach could make its way to clinical application for chronic non-healing DFU.…”

“…miRs are a family of non-coding small ∼22 nt RNAs that regulate gene expression at the post-translational level, with the functional implications in a wide range of biological processes including cutaneous wound healing. [11][12][13][14][15] The function of miRs has also been explored in the context of somatic cell reprogramming. [16][17][18][19] A diverse number of miR regulated processes including apoptosis, senescence and mesenchymal-epithelial transition have been characterized and confirmed to modulate reprogramming in combination with the transcription factors.…”

New Insights on the Effects of Dietary Omega-3 Fatty Acids on Impaired Skin Healing in Diabetes and Chronic Venous Leg Ulcers

“…An exhaustive review was recently published on the topic of the epigenetic regulation of macrophage function during normal and impaired WH [87]. The increasing interest in this issue is demonstrated by the large number of recently published papers analyzed in that review.…”

Skin epigenetics

“…The Tomic-Canic group also provides a comprehensive review of epigenetic regulation of cellular function in wound healing. 41 Addressing the multiple cell types involved in wound healing, the authors discuss epigenetic mechanisms in different cell types and argue for the role of epigenetic deregulation in chronic wounds. Their work suggests that chronic wounds are an important potential target for treatments directed at epigenetic mechanisms.…”