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甲基化 miRNA 可能成为化脓性汗腺炎的潜在生物标志物和治疗靶点。

Methylated miRNAs may serve as potential biomarkers and therapeutic targets for hidradenitis suppurativa.

机构信息

Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, USA.

Department of Life Sciences, School of Sciences, Gujarat University, Ahmedabad, India.

出版信息

J Eur Acad Dermatol Venereol. 2022 Nov;36(11):2199-2213. doi: 10.1111/jdv.18473.

DOI:10.1111/jdv.18473
PMID:35921387
Abstract

BACKGROUND

Hidradenitis suppurativa (HS) is a chronic inflammatory disease influenced by genetics, non-genetic and environmental factors that modulate miRNA expression. Currently, no miRNA data are available for HS. In this study, we profiled DNA methylation patterns of miRNA genes associated with HS susceptibility.

OBJECTIVES

Identify miRNA gene methylation profiles associated with HS susceptibility. This study examined the methylation patterns of DNAs from 24 healthy controls and 24 patients with HS using Illumina Infinium MethylationEPIC BeadChip array analysis. Methylation patterns of miRNA genes were analysed using KEGG pathway analysis to explore the inversely correlated pathways regulated by miRNAs.

RESULTS

We identified 60 CpG sites representing 65 unique microRNA genes including 54 hypomethylated and 6 hypermethylated CpGs as potentially associated with HS. Some of these CpGs were found to be critical for skin function, such as miR-29, miR-200, miR-205, miR-548 and miR-132. The miR-192 is implicated in non-alcoholic fatty liver disease. The miR-200c gene was identified as a vital determinant in regulating skin repair after injury and may contribute to age-associated alterations in wound repair. miR-132 was significantly upregulated during the inflammation phase of wound repair, enhancing the activity of STAT3 and ERK pathways that promote keratinocyte proliferation.

CONCLUSIONS

Epigenetically altered microRNA genes are implicated in wound healing, inflammation, keratinocyte proliferation and wound modulation. This is the first study to analyse methylation profiles of miRNA genes in the HS population, highlighting the unique role that miRNAs might play in diagnosing and treating HS.

摘要

背景

化脓性汗腺炎(HS)是一种受遗传、非遗传和环境因素影响的慢性炎症性疾病,这些因素调节 miRNA 的表达。目前,HS 尚无 miRNA 数据。在这项研究中,我们分析了与 HS 易感性相关的 miRNA 基因的 DNA 甲基化模式。

目的

确定与 HS 易感性相关的 miRNA 基因甲基化谱。本研究使用 Illumina Infinium MethylationEPIC BeadChip 阵列分析,检查了 24 名健康对照者和 24 名 HS 患者的 DNA 甲基化模式。使用 KEGG 途径分析分析 miRNA 基因的甲基化模式,以探讨受 miRNA 调节的反向相关途径。

结果

我们确定了 60 个 CpG 位点,代表 65 个独特的 miRNA 基因,包括 54 个低甲基化和 6 个高甲基化的 CpG,这些 CpG 可能与 HS 相关。其中一些 CpG 对皮肤功能至关重要,如 miR-29、miR-200、miR-205、miR-548 和 miR-132。miR-192 与非酒精性脂肪性肝病有关。miR-200c 基因被确定为调节损伤后皮肤修复的重要决定因素,可能有助于与年龄相关的伤口修复改变。miR-132 在伤口修复的炎症阶段显著上调,增强了促进角质细胞增殖的 STAT3 和 ERK 途径的活性。

结论

表观遗传改变的 miRNA 基因参与伤口愈合、炎症、角质细胞增殖和伤口调节。这是首次分析 HS 人群中 miRNA 基因的甲基化谱,强调了 miRNA 在诊断和治疗 HS 中的独特作用。

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