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

Abstract

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.

Deciphering the molecular nexus between Omicron infection and acute kidney injury: a bioinformatics approach

“…In the context of establishing the relationship between DEGs and miRNAs, we have identified hsa-miR-129-2-3p, hsa-miR-130a-3p, hsa-miR-133a-3p, hsa-miR-146a-5p, and hsa-miR-124-3p as being significantly associated with the pathogenesis and exacerbation of Omicron infections and AKI. Previous investigations have linked these specific miRNAs to the progression and development of various inflammation-associated diseases, including asthma, chronic obstructive pulmonary disease, and colitis ( Lindner et al, 2018 ; Zhai et al, 2020 ; Alamro et al, 2022 ; Qian et al, 2023a ; Chen A. et al, 2023 ), thereby underscoring their potential roles in the context of Omicron infection and AKI. While our analysis sheds light on the potential involvement of these TFs and miRNAs, further experimental studies are imperative to validate their functional significance in the realm of Omicron infection and AKI.…”