Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis
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...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183871/full |
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| author | Anning Chen Zhun Sun Donglin Sun Meiying Huang Hongwei Fang Jinyuan Zhang Guojun Qian |
| author_facet | Anning Chen Zhun Sun Donglin Sun Meiying Huang Hongwei Fang Jinyuan Zhang Guojun Qian |
| author_sort | Anning Chen |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T10:28:24Z |
| publishDate | 2023-05-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-ebf2019ce1d345eb96586d66f9d2e5572023-05-19T04:53:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11838711183871Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary FibrosisAnning Chen0Zhun Sun1Donglin Sun2Meiying Huang3Hongwei Fang4Jinyuan Zhang5Guojun Qian6Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaDepartment of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Pain, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaAffiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, ChinaBackgroundIdiopathic 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183871/fullIdiopathic Pulmonary Fibrosischromatin-modifying enzymesdisease biomarkerhub genesgene ontologydrug molecule |
| spellingShingle | Anning Chen Zhun Sun Donglin Sun Meiying Huang Hongwei Fang Jinyuan Zhang Guojun Qian Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis Frontiers in Immunology Idiopathic Pulmonary Fibrosis chromatin-modifying enzymes disease biomarker hub genes gene ontology drug molecule |
| title | Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis |
| title_full | Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis |
| title_fullStr | Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis |
| title_full_unstemmed | Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis |
| title_short | Integrative bioinformatics and validation studies reveal KDM6B and its associated molecules as crucial modulators in Idiopathic Pulmonary Fibrosis |
| title_sort | integrative bioinformatics and validation studies reveal kdm6b and its associated molecules as crucial modulators in idiopathic pulmonary fibrosis |
| topic | Idiopathic Pulmonary Fibrosis chromatin-modifying enzymes disease biomarker hub genes gene ontology drug molecule |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1183871/full |
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