Identification of PDK4 as Hub Gene for Diabetic Nephropathy Using Co-Expression Network Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37385224", "kind": "science-record", "revision": 4, "content_hash": "sha256:662029def275046ed8b1e30c566d37e5a3c07abd4eaa96893d8bf48fc6b36c2b", "created_at": "2026-11-01T19:02:08Z", "updated_at": "2026-11-01T22:52:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of PDK4 as Hub Gene for Diabetic Nephropathy Using Co-Expression Network Analysis.", "doi": "10.1159/000531288", "pmid": "37385224", "authors": ["Yuanyuan Han", "Liangzi Jin", "Liangzhi Wang", "Lan Wei", "Chao Tu"], "journal": "Kidney & blood pressure research", "year": 2023, "abstract": "INTRODUCTION: Diabetic nephropathy (DN) is related to type 1 and type 2 diabetes. They are the leading cause of end-stage renal disease, but the underling specific pathogenesis of DN is not yet clear. Our study was conducted to explore how DN changed the transcriptome profiles in the kidney.\nMETHODS: The gene expression profile of microdissected glomeruli of 41 type 2 DN patients and 20 healthy controls were included. The sample dataset GSE96804 was obtained from the GEO database. Differentially expressed genes (DEGs) were analyzed in R with the limma package and the important modules were found by weighted gene co-expression network analysis (WGCNA) clustering. The modules were then analyzed based on Gene Ontology (GO) gene set enrichment analysis, and the hub genes were found out. We next validated the hub gene, PDK4, in a cell model of DN. We also constructed the PDK4-related PPI network to investigate the correlation between PDK4 expression and other genes.\nRESULTS: Heatmap and volcano map were drawn to illustrate the mRNA expression profile of 1,204 DEGs in both samples of DN patients and the control group. Using WGCNA, we selected the blue module in which genes showed the strongest correlation with the phenotype and the smallest p value. We also identified PDK4 as a hub gene. PDK4 expression was upregulated in human diabetic kidney tissue. Moreover, PDK4 was speculated to play a role in glomerular basement membrane development and kidney development according to the enrichment of functions and signaling pathways. Furthermore, PDK4 and two key genes GSTA2 and G6PC protein expression were verified highly expressed in the cell model of DN.\nCONCLUSION: During the pathogenesis of DN, many genes may change expression in a coordinated manner. The discovery of PDK4 as key gene using WGCNA is of great significance for the development of new treatment strategies to block the development of DN.", "claims": [{"id": "claim-method", "statement": "The linear model of microarray analysis (limma) was used for the analysis procedure, and the significant DEGs were identified based on the false discovery rate cutoff value <0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37385224", "locator": "sections[3] \"Genome-Wide Gene Expression Profiling and Identification of DEGs\" paragraph 2", "quote": "The linear model of microarray analysis (limma) was used for the analysis procedure, and the significant DEGs were identified based on the false discovery rate cutoff value <0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during the current study are available in the GSE96804 from GEO repository, https://www.ncbi.nlm.nih.gov/geo/. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37385224", "locator": "sections[25] \"Data Availability Statement\" paragraph 2", "quote": "The datasets generated during the current study are available in the GSE96804 from GEO repository, https://www.ncbi.nlm.nih.gov/geo/. Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Heatmap and volcano map were drawn to illustrate the mRNA expression profile of 1,204 DEGs in both samples of DN patients and the control group.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37385224", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Heatmap and volcano map were drawn to illustrate the mRNA expression profile of 1,204 DEGs in both samples of DN patients and the control group."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Heatmap and volcano map were drawn to illustrate the mRNA expression profile of 1,204 DEGs in both samples of DN patients and the control group.", "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:37385224"], "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 gene ex", "< 0.05 considered statistically significant. Transcriptomic Profiles Drastically Altered in DN Patients"], "order_basis": "paper_text_order:309", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d by the R package of corrgram and corrplot. Western blot results were shown as the mean ± SEM. Compar", "itative real-time polymerase chain reaction. Western blotting showed that when the glucose concentration i", "itative real-time polymerase chain reaction. Western blot showed that PDK4 expression continued to dec"], "order_basis": "paper_text_order:2146", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["tes contribute to the progression of DN, the mouse podocyte line is a commonly used cell model"], "order_basis": "paper_text_order:5639", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ifferent concentrations of glucose for 24 h. Flow cytometry confirmed that DN was successfully induced i", "tly lower than those in the control group. b Flow cytometry confirmed that DN was successfully induced i"], "order_basis": "paper_text_order:5923", "id": "assay:4"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["induced in the cultured podocytes, in which apoptosis was significantly increased in the glucose g"], "order_basis": "paper_text_order:6018", "id": "assay:5"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The linear model of microarray analysis (limma) was used for the analysis procedure, and the significant DEGs were identified based on the false discovery rate cutoff value <0.05."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}