The epigenetics of keloids

Abstract

Keloid scarring is a fibroproliferative disorder of the skin of unknown pathophysiology, characterised by fibrotic tissue that extends beyond the boundaries of the original wound. 1 Keloids develop as a result of disturbance to skin architecture by any wound, and have a strong genetic component, appearing in ethnicities with darker skin pigmentation. 1 There are estimated to be over 11 million keloids in the developed world, with the global number unknown but expected to be higher. 2 Current dogma suggests keloid development follows a similar pathway to normal wound healing but with chronic progression, suggesting disturbance in the fine control of cellular functions that occur during wound healing. 3 Epigenetics, defined as non-base-pair sequence alterations to the DNA, is a key regulator of cell functions, and aberrant epigenetic modifications have been found to contribute to many pathologies, including keloid scars. Our knowledge of progressive fibrosis remains limited, and therapeutic options are few and commonly ineffective, with keloids commonly recurring even after surgery and adjunct treatments. There is an urgent need to gain critical knowledge that will allow us to design better therapeutic strategies and provide evidence to support clinical decisions. This review will explore the current knowledge of the contribution of epigenetic modifications such as DNA methylation, histone modification, microRNAs, long non-coding RNAs to keloid scar formation and progression, and potential treatments utilising modifiers of these processes.

Inhibition of miR-23b-3p Ameliorates Scar-Like Phenotypes of Keloid Fibroblasts by Facilitating A20 Expression

“…Increasing evidence has demonstrated that miRNAs are involved in the modulation of biological function of fibroblast, which further contributes to pathogenesis of keloid. 9 In the present study, we verified the upregulation of miR-23b-3p existed in keloid tissues, primary KFs and KF cell line KEL FIB cells, which was in line with the previous bioinformatics analysis. 13 Currently, studies about miR-23b-3p mostly concentrate on tumors.…”

“… 8 Moreover, accumulating evidence has stated that miRNAs are implicated in the regulation of biological phenotypes of fibroblasts to participate in the pathogenesis of keloid. 9 Liu et al reported that the miR-21 was upregulated in keloid tissues, and inhibition of miR-21 accelerated apoptosis of KFs by relieving the suppression to FasL, a proapoptotic molecule. 10 An in vitro and in vivo study suggested that decreased expression of miR-21 could be regarded as a molecular biomarker that reflected the effectiveness of treatment of Galla Chinensis for keloid.…”

Detection and analysis of long noncoding RNA expression profiles related to epithelial–mesenchymal transition in keloids

“…Transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) and the renin–angiotensin system were reported to be potential targets in keloid management considering their participation in wound healing and keloid formation [ 3 , 4 ]. In addition, miRNA modulation may be a novel therapeutic solution [ 5 ]. However, neither first-line therapies nor developing treatments could guarantee satisfying curative effects, which calls for more research on effective targets.…”

Translational Research Techniques for the Facial Plastic Surgeon: An Overview

“…They found 79,305 CpG sites within promoter regions that were hypermethylated. This may be why global inhibitors of methylation such as 5-azacytdine have shown a promising treatment potential for keloids 59 . Future studies may be conducted to develop therapeutics to alter the methylation profile and epigenetic changes for KD and various other disease states.…”