Genetics and Epigenetics of Keloids

Nyika, Dennias Tonderai; Khumalo, Nonhlanhla P.; Bayat, Ardeshir

doi:10.1089/wound.2021.0094

Cited by 17 publications

(14 citation statements)

References 45 publications

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“…In another study involving 15 keloid samples, mutations in exons of the p53 gene were discovered in all keloid samples [ 40 ]. In addition, the importance of the HLA haplotype in the process of keloid fibrosis has been verified in relevant studies [ 41 ]. In studies on the association between the HLA system and keloids, the risk of keloid development in Caucasians was positively correlated with the frequency of the HLA-DRB1*15 phenotype, and the distribution of HLA-DQA1 and DQB1 alleles was enormously disparate between keloid and normal populations in the analysis of Chinese Han keloid patients [ 42 , 43 ].…”

Section: Reviewmentioning

confidence: 99%

Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

et al. 2022

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Keloid scarring is a kind of pathological healing manifestation after skin injury and possesses various tumor properties, such as the Warburg effect, epithelial–mesenchymal transition (EMT), expression imbalances of apoptosis-related genes and the presence of stem cells. Abnormal expression of tumor signatures is critical to the initiation and operation of these effects. Although previous experimental studies have recognized the potential value of a single or several tumor biomolecules in keloids, a comprehensive evaluation system for multiple tumor signatures in keloid scarring is still lacking. This paper aims to summarize tumor biomolecules in keloids from the perspectives of liquid biopsy, genetics, proteomics and epigenetics and to investigate their mechanisms of action and feasibility from bench to bedside. Liquid biopsy is suitable for the early screening of people with keloids due to its noninvasive and accurate performance. Epigenetic biomarkers do not require changes in the gene sequence and their reversibility and tissue specificity make them ideal therapeutic targets. Nonetheless, given the ethnic specificity and genetic predisposition of keloids, more large-sample multicenter studies are indispensable for determining the prevalence of these signatures and for establishing diagnostic criteria and therapeutic efficacy estimations based on these molecules.

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Section: Reviewmentioning

confidence: 99%

Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

et al. 2022

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“…Histone modification refers to the processes such as methylation, acetylation, phosphorylation, adenylation, ubiquitination, and ADP ribosylation by related enzymes ( Wang et al, 2016a ). DNA methylation is involved in keloid formation, and includes processes such as cell proliferation, invasion of myofibroblasts, activation of collagen deposition and disorder ( Nyika et al, 2022 ). Russell et al found that abnormal DNA methylation and histone acetylation modification of keloid fibroblasts can affect the stability of gene expression, and DNA methylation of HOXA9 and HOXA10 can alter the wound healing ability of keloid fibroblasts ( Russell et al, 2010 ).…”

Section: Keloid Pathogenesis Studymentioning

confidence: 99%

Biomechanical Regulatory Factors and Therapeutic Targets in Keloid Fibrosis

et al. 2022

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Keloids are fibroproliferative skin disorder caused by abnormal healing of injured or irritated skin and are characterized by excessive extracellular matrix (ECM) synthesis and deposition, which results in excessive collagen disorders and calcinosis, increasing the remodeling and stiffness of keloid matrix. The pathogenesis of keloid is very complex, and may include changes in cell function, genetics, inflammation, and other factors. In this review, we aim to discuss the role of biomechanical factors in keloid formation. Mechanical stimulation can lead to excessive proliferation of wound fibroblasts, deposition of ECM, secretion of more pro-fibrosis factors, and continuous increase of keloid matrix stiffness. Matrix mechanics resulting from increased matrix stiffness further activates the fibrotic phenotype of keloid fibroblasts, thus forming a loop that continuously invades the surrounding normal tissue. In this process, mechanical force is one of the initial factors of keloid formation, and matrix mechanics leads to further keloid development. Next, we summarized the mechanotransduction pathways involved in the formation of keloids, such as TGF-β/Smad signaling pathway, integrin signaling pathway, YAP/TAZ signaling pathway, and calcium ion pathway. Finally, some potential biomechanics-based therapeutic concepts and strategies are described in detail. Taken together, these findings underscore the importance of biomechanical factors in the formation and progression of keloids and highlight their regulatory value. These findings may help facilitate the development of pharmacological interventions that can ultimately prevent and reduce keloid formation and progression.

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“…Untimely, cessation of this process leads to excessive accumulation of fibrotic tissue and formation of, e.g., hypertrophic/keloid scarring. However, keloid formation also requires certain genetic susceptibility (Nyika et al 2022).…”

Section: Skin Injury -An Example Of a Simple Healing Processmentioning

confidence: 99%

Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation

Gál

Brábek

Holub

et al. 2022

Histochem Cell Biol

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Recent evidence indicates that targeting IL-6 provides broad therapeutic approaches to several diseases. In patients with cancer, autoimmune diseases, severe respiratory infections [e.g. coronavirus disease 2019 (COVID-19)] and wound healing, IL-6 plays a critical role in modulating the systemic and local microenvironment. Elevated serum levels of IL-6 interfere with the systemic immune response and are associated with disease progression and prognosis. As already noted, monoclonal antibodies blocking either IL-6 or binding of IL-6 to receptors have been used/tested successfully in the treatment of rheumatoid arthritis, many cancer types, and COVID-19. Therefore, in the present review, we compare the impact of IL-6 and anti-IL-6 therapy to demonstrate common (pathological) features of the studied diseases such as formation of granulation tissue with the presence of myofibroblasts and deposition of new extracellular matrix. We also discuss abnormal activation of other wound-healing-related pathways that have been implicated in autoimmune disorders, cancer or COVID-19.

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Genetics and Epigenetics of Keloids

Cited by 17 publications

References 45 publications

Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

Advances in the pathogenesis and clinical application prospects of tumor biomolecules in keloid

Biomechanical Regulatory Factors and Therapeutic Targets in Keloid Fibrosis

Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation

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