Qing Yuxin, Wu Jiawen, Xu Bingyang, Xu Zining, Ye Shuhong, Wang Yuanqin, Zhao Bin, Sun Hong, Wu Na
Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Clinical Medicine, The Second Clinical Medical College Affiliated to Xi'an Jiaotong University, Xi'an, China.
Inflammation. 2025 Mar 4. doi: 10.1007/s10753-025-02278-5.
Endoplasmic reticulum stress (ERS) has recently been proposed as a core factor in the pathogenesis and aggravation of rosacea. The roles of ERS-related genes in rosacea are largely unknown and were investigated in this study. Rosacea microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed ERS-related genes in rosacea patients vs. controls were screened using the Limma package, and LASSO regression was used to screen for characteristic genes. The infiltrating fraction was evaluated using ssGSEA. Clinical rosacea samples, age-matched healthy volunteers, and LL37-induced mice models were used to investigate the expression of DNAJB2 and its function. In the GSE65914 dataset, 17 differentially expressed ERS-related genes were screened. Of these, 13 were identified as characteristic genes predicting rosacea risk. The adaptive immune response, TLR signaling pathway, and chemokine signaling pathway were activated with a high risk of rosacea. After expression validation using the GSE155141 dataset, DNAJB2 was identified as a key gene. DNAJB2 expression was significantly decreased in both datasets, clinical samples, and the LL37-induced mice model. DNAJB2 overexpression could alleviate rosacea skin injury and inhibit expression of inflammatory cytokines and chemokines as well as angiogenesis. The infiltration levels of the majority of immune cell types were elevated in rosacea samples, and DNAJB2 overexpression inhibited CD4 + T cell infiltration, as well as Th1 and Th17 polarizing genes. Moreover, DNAJB2 could inhibit ERS marker proteins and the activated TLR2/Myd88/NF-κB pathway. DNAJB2 may be a novel target for rosacea treatment.
内质网应激（ERS）最近被认为是酒渣鼻发病机制和病情加重的核心因素。ERS相关基因在酒渣鼻中的作用在很大程度上尚不清楚，本研究对其进行了探究。从基因表达综合数据库（GEO）下载酒渣鼻微阵列数据集。使用Limma软件包筛选酒渣鼻患者与对照组中差异表达的ERS相关基因，并使用LASSO回归筛选特征基因。采用单样本基因集富集分析（ssGSEA）评估浸润分数。利用临床酒渣鼻样本、年龄匹配的健康志愿者以及LL37诱导的小鼠模型来研究DNAJB2的表达及其功能。在GSE65914数据集中，筛选出17个差异表达的ERS相关基因。其中，13个被确定为预测酒渣鼻风险的特征基因。适应性免疫反应、Toll样受体（TLR）信号通路和趋化因子信号通路在酒渣鼻高风险时被激活。通过GSE155141数据集进行表达验证后，DNAJB2被确定为关键基因。在这两个数据集、临床样本以及LL37诱导的小鼠模型中，DNAJB2表达均显著降低。DNAJB2过表达可减轻酒渣鼻皮肤损伤，抑制炎性细胞因子、趋化因子的表达以及血管生成。酒渣鼻样本中大多数免疫细胞类型的浸润水平升高，DNAJB2过表达可抑制CD4 + T细胞浸润以及Th1和Th17极化基因。此外，DNAJB2可抑制ERS标记蛋白以及激活的TLR2/髓样分化因子88（Myd88）/核因子κB（NF-κB）通路。DNAJB2可能是酒渣鼻治疗的新靶点。
