Table_1_Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis.xlsx

BackgroundIdiopathic Pulmonary Fibrosis (IPF) can be described as a debilitating lung disease that is characterized by the complex interactions between various immune cell types and signaling pathways. Chromatin-modifying enzymes are significantly involved in regulating gene expression during immune cell development, yet their role in IPF is not well understood.
MethodsIn this study, differential gene expression analysis and chromatin-modifying enzyme-related gene data were conducted to identify hub genes, common pathways, immune cell infiltration, and potential drug targets for IPF. Additionally, a murine model was employed for investigating the expression levels of candidate hub genes and determining the infiltration of different immune cells in IPF.
ResultsWe identified 33 differentially expressed genes associated with chromatin-modifying enzymes. Enrichment analyses of these genes demonstrated a strong association with histone lysine demethylation, Sin3-type complexes, and protein demethylase activity. Protein-protein interaction network analysis further highlighted six hub genes, specifically KDM6B, KDM5A, SETD7, SUZ12, HDAC2, and CHD4. Notably, KDM6B expression was significantly increased in the lungs of bleomycin-induced pulmonary fibrosis mice, showing a positive correlation with fibronectin and α-SMA, two essential indicators of pulmonary fibrosis. Moreover, we established a diagnostic model for IPF focusing on KDM6B and we also identified 10 potential therapeutic drugs targeting KDM6B for IPF treatment.
ConclusionOur findings suggest that molecules related to chromatin-modifying enzymes, primarily KDM6B, play a critical role in the pathogenesis and progression of IPF.

背景
特发性肺纤维化（Idiopathic Pulmonary Fibrosis, IPF）是一种致残性肺部疾病，其特征为多种免疫细胞类型与信号通路间的复杂相互作用。染色质修饰酶（chromatin-modifying enzymes）在免疫细胞发育过程中显著参与调控基因表达，但其在IPF中的作用尚未明确。
方法
本研究通过差异基因表达分析及染色质修饰酶相关基因数据，旨在鉴定IPF的核心基因、共同通路、免疫细胞浸润特征及潜在药物靶点。此外，本研究采用小鼠模型，以探究候选核心基因的表达水平，并明确IPF中不同免疫细胞的浸润情况。
结果
本研究共鉴定出33个与染色质修饰酶相关的差异表达基因。对这些基因的富集分析显示，其与组蛋白赖氨酸去甲基化、Sin3型复合物及蛋白质去甲基化酶活性存在强关联。蛋白质-蛋白质相互作用网络分析进一步筛选出6个核心基因，分别为KDM6B、KDM5A、SETD7、SUZ12、HDAC2及CHD4。值得注意的是，博莱霉素诱导的肺纤维化小鼠肺部中KDM6B的表达显著升高，且与肺纤维化的两个关键指标——纤连蛋白（fibronectin）和α-平滑肌肌动蛋白（α-SMA）呈正相关。此外，本研究构建了以KDM6B为核心的IPF诊断模型，并鉴定出10种靶向KDM6B用于IPF治疗的潜在治疗药物。
结论
本研究结果表明，与染色质修饰酶相关的分子（主要为KDM6B）在IPF的发病机制与疾病进展中发挥关键作用。