Summary Background The absence of melanocytes poses a challenge for long‐term tissue homeostasis in vitiligo. Surprisingly, while individuals with Fitzpatrick phototypes I–II (low melanin content) have a higher incidence of melanoma and nonmelanoma skin cancer, people with vitiligo are at a decreased risk for the same. Objectives To understand the molecular mechanisms that protect vitiligo skin from ultraviolet (UV)‐induced DNA damage by (i) characterizing differentially expressed microRNAs in lesional vs. nonlesional epidermis and (ii) identifying their upstream regulators and downstream gene targets. Methods Genome‐wide microRNA profiling of nonlesional and lesional epidermis was performed on five individuals with stable nonsegmental vitiligo using next‐generation RNA sequencing. The relevance of the upstream regulator and downstream target gene of the most differentially expressed microRNA was studied. Results Our study found sirtuin1 (SIRT1), an NAD‐dependent deacetylase, to be a direct target of miR‐211 – the most significantly downregulated microRNA in lesional epidermis. Inhibition of SIRT1 with EX‐527 downregulated keratin 10 and involucrin, suggesting that SIRT1 promotes keratinocyte differentiation. Overexpression of miR‐211 mimic led to a significant increase in γ‐H2AX positivity and cyclobutane pyrimidine dimer (CPD) formation, hallmarks of UVB‐mediated DNA damage. These effects could be ameliorated by the addition of resveratrol, a SIRT1 activator. Furthermore, a long noncoding RNA, MALAT1, was identified as a negative upstream regulator of miR‐211. Overexpression of MALAT1 resulted in increased expression of SIRT1 and a concomitant removal of UVB‐induced CPDs in primary keratinocytes. Conclusions These findings establish a novel MALAT1–miR‐211–SIRT1 signalling axis that potentially confers protection to the ‘amelanotic’ keratinocytes in vitiligo.
Although the impairment of quality of life (QoL) in individuals with keloids is profound, it has neither been well quantified nor correlated with severity in people with skin of colour. This cross-sectional, questionnaire-based study comprised 110 patients with keloid(s). A physician measured the severity of keloids using the Vancouver Scar scale and impairment of QoL using the patient-filled Hindi version of Dermatology Life Quality Index questionnaire. The relationship among QoL and severity score as well as with components of demographic data was analysed using SPSS. Our study found the severity of keloid(s) to be moderately but significantly correlated with the QoL of its sufferers.Individuals with multiple keloids were found to be significantly younger than those with solitary ones. Itching, pain, along with restricted mobility significantly impacted the QoL as well as severity of keloids. Individuals who had undergone prior treatment were found to have a worse QoL than the treatment naive. Recurrence was found to be associated with lower scar severity, multiple keloids, and younger age. Increasing age, though associated with greater scar severity, lacked any relationship with the QoL. Our study also found that individuals with bigger keloids sought treatment earlier and more often. Hyperpigmented keloid(s), more common in individuals with skin of colour, were associated with a significantly worse QoL and a higher scar severity.keloid, quality of life, severity, skin of colour | INTRODUCTIONKeloidsclaw-like irregular deposition of dense fibrous tissue beyond the edges of the original injuryrepresent an exaggerated healing response in predisposed individuals. 1 Located most often on the chest, shoulders, upper back, posterior neck, and earlobes, keloids occur more commonly in people with darker skin -African Americans, Hispanics, and Asians. 2,3,4 However, treatment options of this relatively common condition continue to focus on improving cosmesis and alleviating symptoms, such as pruritus, pain, and loss of function, rather than on a complete cure. 5 Individuals with visible keloids often experience stigmatisation, reduced body esteem, and some degree of social isolation. 6 In the current era of heightened aesthetic awareness, keloidal scarring can greatly affect the self-perception of patients and impair their quality of life (QoL); thus, measuring the latter, is becoming increasingly important in contemporary clinical dermatology. However, little is known about the impact of these scars on the QoL of its patients; some Western studies that have Abbreviations: ANOVA, analysis of variance test
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