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OMICS Approaches Evaluating Keloid and Hypertrophic Scars.

ABSTRACT: Abnormal scar formation during wound healing can result in keloid and hypertrophic scars, which is a major global health challenge. Such abnormal scars can cause significant physiological pain and psychological distress and become a financial burden. Due to the biological complexity of scar formation, the pathogenesis of such scars and how to prevent them from forming remains elusive. In this review paper, we delve into the world of "omics" approaches to study abnormal scars and provide examples of genomics, transcriptomics, proteomics, epigenomics, and metabolomics. The benefits of "omics" approaches are that they allow for high-throughput studies and the analysis of 100s to 1000s of genes and proteins with the accumulation of large quantities of data. Currently in the field, there is a lack of "omics" review articles describing pathological scars. In this review, we summarize genome-wide linkage analysis, genome-wide association studies, and microarray data to name a few omics technologies. Such data can provide novel insights into different molecular pathways and identify novel factors which may not be captured through small-scale laboratory techniques.

SUBMITTER: Bakhtyar N

PROVIDER: S-EPMC9722497 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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OMICS Approaches Evaluating Keloid and Hypertrophic Scars.

Bakhtyar Nazihah N Amini-Nik Saeid S Jeschke Marc G MG

International journal of inflammation 20221027

Abnormal scar formation during wound healing can result in keloid and hypertrophic scars, which is a major global health challenge. Such abnormal scars can cause significant physiological pain and psychological distress and become a financial burden. Due to the biological complexity of scar formation, the pathogenesis of such scars and how to prevent them from forming remains elusive. In this review paper, we delve into the world of "omics" approaches to study abnormal scars and provide examples ...[more]

PMID: 36483731

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Project description:ImportanceKeloids and hypertrophic scars (excessive scarring) are relatively understudied disfiguring chronic skin conditions with high treatment resistance.ObjectiveTo evaluate established comorbidities of excessive scarring in European individuals, with comparisons across ethnic groups, and to identify novel comorbidities via a phenome-wide association study (PheWAS).Design, setting, and participantsThis multicenter cross-sectional population-based cohort study used UK Biobank (UKB) data and fitted logistic regression models for testing associations between excessive scarring and a variety of outcomes, including previously studied comorbidities and 1518 systematically defined disease categories. Additional modeling was performed within subgroups of participants defined by self-reported ethnicity (as defined in UK Biobank). Of 502 701 UKB participants, analyses were restricted to 230078 individuals with linked primary care records.ExposuresKeloid or hypertrophic scar diagnoses.Main outcomes and measuresPreviously studied disease associations (hypertension, uterine leiomyoma, vitamin D deficiency, atopic eczema) and phenotypes defined in the PheWAS Catalog.ResultsOf the 972 people with excessive scarring, there was a higher proportion of female participants compared with the 229 106 controls (65% vs 55%) and a lower proportion of White ethnicity (86% vs 95%); mean (SD) age of the total cohort was 64 (8) years. Associations were identified with hypertension and atopic eczema in models accounting for age, sex, and ethnicity, and the association with atopic eczema (odds ratio [OR], 1.68; 95% CI, 1.36-2.07; P < .001) remained statistically significant after accounting for additional potential confounders. Fully adjusted analyses within ethnic groups revealed associations with hypertension in Black participants (OR, 2.05; 95% CI, 1.13-3.72; P = .02) and with vitamin D deficiency in Asian participants (OR, 2.24; 95% CI, 1.26-3.97; P = .006). The association with uterine leiomyoma was borderline significant in Black women (OR, 1.93; 95% CI, 1.00-3.71; P = .05), whereas the association with atopic eczema was significant in White participants (OR, 1.68; 95% CI, 1.34-2.12; P < .001) and showed a similar trend in Asian (OR, 2.17; 95% CI, 1.01-4.67; P = .048) and Black participants (OR, 1.89; 95% CI, 0.83-4.28; P = .13). The PheWAS identified 110 significant associations across disease systems; of the nondermatological, musculoskeletal disease and pain symptoms were prominent.Conclusions and relevanceThis cross-sectional study validated comorbidities of excessive scarring in UKB with comprehensive coverage of health outcomes. It also documented additional phenome-wide associations that will serve as a reference for future studies to investigate common underlying pathophysiologic mechanisms.

Project description:Keloids and hypertrophic scars are caused by cutaneous injury and irritation, including trauma, insect bite, burn, surgery, vaccination, skin piercing, acne, folliculitis, chicken pox, and herpes zoster infection. Notably, superficial injuries that do not reach the reticular dermis never cause keloidal and hypertrophic scarring. This suggests that these pathological scars are due to injury to this skin layer and the subsequent aberrant wound healing therein. The latter is characterized by continuous and histologically localized inflammation. As a result, the reticular layer of keloids and hypertrophic scars contains inflammatory cells, increased numbers of fibroblasts, newly formed blood vessels, and collagen deposits. Moreover, proinflammatory factors, such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α are upregulated in keloid tissues, which suggests that, in patients with keloids, proinflammatory genes in the skin are sensitive to trauma. This may promote chronic inflammation, which in turn may cause the invasive growth of keloids. In addition, the upregulation of proinflammatory factors in pathological scars suggests that, rather than being skin tumors, keloids and hypertrophic scars are inflammatory disorders of skin, specifically inflammatory disorders of the reticular dermis. Various external and internal post-wounding stimuli may promote reticular inflammation. The nature of these stimuli most likely shapes the characteristics, quantity, and course of keloids and hypertrophic scars. Specifically, it is likely that the intensity, frequency, and duration of these stimuli determine how quickly the scars appear, the direction and speed of growth, and the intensity of symptoms. These proinflammatory stimuli include a variety of local, systemic, and genetic factors. These observations together suggest that the clinical differences between keloids and hypertrophic scars merely reflect differences in the intensity, frequency, and duration of the inflammation of the reticular dermis. At present, physicians cannot (or at least find it very difficult to) control systemic and genetic risk factors of keloids and hypertrophic scars. However, they can use a number of treatment modalities that all, interestingly, act by reducing inflammation. They include corticosteroid injection/tape/ointment, radiotherapy, cryotherapy, compression therapy, stabilization therapy, 5-fluorouracil (5-FU) therapy, and surgical methods that reduce skin tension.

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OMICS Approaches Evaluating Keloid and Hypertrophic Scars.

Publications

OMICS Approaches Evaluating Keloid and Hypertrophic Scars.

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