Screening and Identification of Hub Genes in the Corticosteroid Resistance Network in Human Airway Epithelial Cells via Microarray Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34707493", "kind": "science-record", "revision": 5, "content_hash": "sha256:2e522fb0a6f9764d16a05c707f6bde8a1063886764205f57dbc85c5d39154580", "created_at": "2026-11-01T17:36:22Z", "updated_at": "2026-11-01T22:47:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening and Identification of Hub Genes in the Corticosteroid Resistance Network in Human Airway Epithelial Cells via Microarray Analysis.", "doi": "10.3389/fphar.2021.672065", "pmid": "34707493", "authors": ["Guangsheng Pei", "Nan Ma", "Fugang Chen", "Liyan Guo", "Jing Bai", "Jingmin Deng", "Zhiyi He"], "journal": "Frontiers in pharmacology", "year": 2021, "abstract": "Background and Objective: Corticosteroid resistance is a major barrier to chronic obstructive pulmonary disease (COPD), but the exact mechanism of corticosteroid resistance in COPD has been less well studied. Methods: The microarray dataset GSE11906, which includes genomic and clinical data on COPD, was downloaded from the Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were identified using R software. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes (KEGG) were utilized to enrich and analyze the gene cohort related to the response to steroid hormones, respectively. The Connectivity Map (CMap) database was used to screen corticosteroid resistance-related drugs that might exert a potential therapeutic effect. STRING was used to construct a protein-protein interaction (PPI) network of the gene cohort, and the CytoHubba plug-in of Cytoscape was used to screen the hub genes in the PPI network. The expression levels of hub genes in cigarette smoke extract (CSE)-stimulated bronchial epithelial cells were assayed by quantitative real-time PCR and western blotting. Results: Twenty-one genes were found to be correlated with the response to steroid hormones. In the CMap database, 32 small-molecule compounds that might exert a therapeutic effect on corticosteroid resistance in COPD were identified. Nine hub genes were extracted from the PPI network. The expression levels of the BMP4, FOS, FN1, EGFR, and SPP1 proteins were consistent with the microarray data obtained from molecular biology experiments. Scopoletin significantly restrained the increases in the levels of AKR1C3, ALDH3A1, FN1 and reversed the decreases of phosphorylated GR and HDAC2 caused by CSE exposure. Conclusion: The BMP4, FOS, FN1, EGFR, and SPP1 genes are closely correlated with CSE-induced glucocorticoid resistance in airway epithelial cells. Scopoletin may be a potential drug for the treatment of glucocorticoid resistance caused by CSE.", "claims": [{"id": "claim-method", "statement": "The “limma” package of R software (version 3.5.1) was used to screen GSE11906 to identify the DEGs, and mRNAs with a P-value < 0.05 were considered to be genes with significant differential expression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34707493", "locator": "sections[4] \"GSEA\" paragraph 2", "quote": "The “limma” package of R software (version 3.5.1) was used to screen GSE11906 to identify the DEGs, and mRNAs with a P-value < 0.05 were considered to be genes with significant differential expression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34707493", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using limma on GSE11906, the study identified 335 differentially expressed genes, including 187 upregulated and 148 downregulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34707493", "locator": "sections[14] \"Identification of Differentially Expressed Genes\" paragraph 2", "quote": "A total of 335 DEGs, including 187 upregulated and 148 downregulated genes, were obtained from GSE11906 using the limma package."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using limma on GSE11906, the study identified 335 differentially expressed genes, including 187 upregulated and 148 downregulated genes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34707493"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Methods: The microarray dataset GSE11906, which includes genomic and", ", and SPP1 proteins were consistent with the microarray data obtained from molecular biology experim"], "order_basis": "paper_text_order:75", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["pithelial cells were assayed by quantitative real-time PCR and western blotting. Results: Twenty-one ge", "d for the extraction of RNA and proteins for qPCR and WB assays, respectively. Statistical Ana", "says, respectively. Statistical Analysis The qPCR and WB data are presented as the means ±SDs."], "order_basis": "paper_text_order:1192", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["re assayed by quantitative real-time PCR and western blotting. 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