Department of Dermatology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
The 2nd Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Exp Dermatol. 2023 Apr;32(4):359-367. doi: 10.1111/exd.14710. Epub 2022 Dec 1.
Mutations in the γ-secretase complex have been well-described in familial hidradenitis suppurativa (HS). No gene mutations have been identified in sporadic HS, which comprises 60%-70% of all HS cases. Obesity and smoking are risk factors for HS and are closely related to DNA methylation, an essential epigenetic phenomenon. Hence, we hypothesized that epigenetic modifications might be involved in sporadic HS. To investigate genes with aberrant methylation in sporadic HS cases and assess their expression in skin lesions and blood from patients with HS. Skin lesion samples and corresponding normal skin were obtained from three patients with HS and subjected to whole-genome DNA methylation sequencing. Blood samples were collected from 20 patients with HS and 20 healthy controls (HCs). The HS mouse model was established by applying tamoxifen to Ncstn mice. Target gene expression was analysed by immunohistochemistry, immunofluorescence, western blotting, enzyme-linked immunosorbent assay (ELISA) and semiquantitative real-time polymerase chain reaction (RT-qPCR). Among 10 807 differentially methylated genes, we filtered 2101 genes with hypermethylated promoter regions, and following bioinformatics analyses, we focused on CXC chemokine ligand 16 (CXCL16). Subsequent functional experiments confirmed the downregulation of CXCL16 and its receptor, CXC chemokine receptor (CXCR) 6, in skin tissue from HS patients and Ncstn mice. Serum CXCL16 concentrations were also significantly decreased in patients with HS. Our data revealed the downregulation of CXCL16 and CXCR6 in HS.
γ-分泌酶复合物的突变已在家族性化脓性汗腺炎（HS）中得到很好的描述。散发性 HS 中尚未发现基因突变，占所有 HS 病例的 60%-70%。肥胖和吸烟是 HS 的危险因素，与 DNA 甲基化密切相关，DNA 甲基化是一种重要的表观遗传现象。因此，我们假设表观遗传修饰可能与散发性 HS 有关。本研究旨在检测散发性 HS 病例中异常甲基化的基因，并评估其在 HS 患者皮肤损伤和血液中的表达。从 3 例 HS 患者的皮肤损伤样本和相应的正常皮肤中提取全基因组 DNA 甲基化测序。收集 20 例 HS 患者和 20 例健康对照者（HCs）的血液样本。通过向 Ncstn 小鼠施用他莫昔芬建立 HS 小鼠模型。通过免疫组织化学、免疫荧光、western blot、酶联免疫吸附试验（ELISA）和半定量实时聚合酶链反应（RT-qPCR）分析靶基因表达。在 10807 个差异甲基化基因中，我们筛选出 2101 个具有超甲基化启动子区域的基因，通过生物信息学分析，我们重点关注 CXC 趋化因子配体 16（CXCL16）。随后的功能实验证实，HS 患者和 Ncstn 小鼠皮肤组织中 CXCL16 及其受体 CXC 趋化因子受体（CXCR）6 的表达下调。HS 患者血清 CXCL16 浓度也显著降低。我们的数据显示 CXCL16 和 CXCR6 在 HS 中下调。
