Identification and experimental validation of mitochondrial and endoplasmic reticulum stress related gene in diabetic nephropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40775242", "kind": "science-record", "revision": 3, "content_hash": "sha256:9c92f6d2c8245f8ea6e1f503f45dea9e9f75b3aa069871686ead7f94a6ce8af8", "created_at": "2026-11-01T20:30:52Z", "updated_at": "2026-11-01T22:14:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and experimental validation of mitochondrial and endoplasmic reticulum stress related gene in diabetic nephropathy.", "doi": "10.1038/s41598-025-11097-5", "pmid": "40775242", "authors": ["Ting Li", "Li Li", "Zijuan Sun", "Huijuan Zeng", "Guoyong He", "Zhong Tian", "Dong Chen", "Jun Li"], "journal": "Scientific reports", "year": 2025, "abstract": "Diabetic nephropathy (DN) is a kidney disease. Mitochondrial and endoplasmic reticulum stress (ERS) significantly contribute to diabetic nephropathy (DN), although the precise mechanisms involved have not yet been fully understood. The objective of this research was to explore the potential of mitochondrial and ERS genes as pivotal genetic elements in individuals with DN and to elucidate their fundamental molecular mechanisms. The datasets GSE30528 and GSE30122 were obtained from the Gene Expression Omnibus (GEO) database. Firstly, differentially expressed genes (DEGs) (DN and control samples) were identified by differential expression analysis. Candidate genes were obtained by intersecting the DEGs with mitochondria and endoplasmic reticulum stress-related genes. The key genes were identified through three machine learning methods, the receiver operating characteristic (ROC) curve analysis and expression validation. Subsequently, a nomogram model for DN was constructed. Moreover, gene set enrichment analysis (GSEA), immune infiltration, molecular regulatory networks of key genes were explored, Later, predicted their drugs. Finally, three key genes (GPX1, PPIF and VDAC1) were identified by expression validation and ROC validation and three key genes were all down-regulated in DN. Meanwhile, RT-qPCR analysis yielded the same results. In addition, the nomogram model of key genes was constructed, and the model had a good prediction effect. GSEA showed that the top 3 most prominent pathways shared by the 3 key genes included oxidative phosphorylation, glutathione metabolism, and ribosome. Immune cells, including gamma-delta T cells, activated mast cells, and M2 macrophages, exhibited differential infiltration between the DN group and the control group. A total of 23 lncRNAs targeting intersecting miRNAs of three key genes. There were 4 drugs associated with the three key genes. In this research, three key genes (GPX1, PPIF and VDAC1) mitochondrial and endoplasmic reticulum stress-related gene in DN were identified, providing a potential theoretical basis for DN treatment. However, this study still has certain limitations. This study only used a single dataset for analysis and validation, so the results of the study may not fully reflect the diversity of DN patients.", "claims": [{"id": "claim-method", "statement": "In GSE30528 and GSE30122, genes with consistent expression trends and significant differences (p < 0.05) between groups were obtained by Wilcoxon test for subsequent analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40775242", "locator": "sections[8] \"Expression validation and receiver operating characteristic (ROC) curve analysis\" paragraph 2", "quote": "In GSE30528 and GSE30122, genes with consistent expression trends and significant differences (p < 0.05) between groups were obtained by Wilcoxon test for subsequent analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available in the GEO repository （http://www.ncbi.nlm.nih.gov/geo/）, The Mitochondrial Protein Reference Set 3.0 (MitoCarta3.0) repository (http://www.broadinstitute.org/mitocarta), and The molecular signatures database (MSigDB, https://www.gsea-msigdb.org/gsea/msigdb/index.jsp).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40775242", "locator": "sections[33] \"Data availability\" paragraph 2", "quote": "The datasets analysed during the current study are available in the GEO repository （http://www.ncbi.nlm.nih.gov/geo/）, The Mitochondrial Protein Reference Set 3.0 (MitoCarta3.0) repository (http://www.broadinstitute.org/mitocarta), and The molecular signatures database (MSigDB, https://www.gsea-msigdb.org/gsea/msigdb/index.jsp)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three genes (GPX1, PPIF, and VDAC1) with significant differences in expression and consistent trends between the DN and control groups were obtained by Wilcoxon test, and all three key genes were down-regulated in DN (p < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "In order to understand the distinctions in the expression of candidate characterized genes in GSE30528 and GSE30122, three genes (GPX1, PPIF, and VDAC1) with significant differences in expression and consistent trends between the DN and control groups were obtained by Wilcoxon test, and three key genes were all down-regulated in DN (p < 0.05) (Fig. 3e)."}, "evidence": [{"asset": "source:pmid:40775242", "locator": "sections[21] \"Identification of biomarker key genes\" paragraph 2", "quote": "In order to understand the distinctions in the expression of candidate characterized genes in GSE30528 and GSE30122, three genes (GPX1, PPIF, and VDAC1) with significant differences in expression and consistent trends between the DN and control groups were obtained by Wilcoxon test, and three key genes were all down-regulated in DN (p < 0.05) (Fig. 3e)."}, {"asset": "source:pmid:40775242", "locator": "sections[21] \"Identification of biomarker key genes\" paragraph 2", "quote": "Next, the ROC curves of the three genes were plotted, and the AUC values of the three genes in GSE30528 and GSE30122 were all exceeding 0.7, which were defined as the key genes (GPX1, PPIF, and VDAC1) to be used as the subsequent analyses (Fig. 3g)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Three genes (GPX1, PPIF, and VDAC1) with significant differences in expression and consistent trends between the DN and control groups were obtained by Wilcoxon test, and all three key genes were down-regulated in DN (p < 0.05).", "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:40775242"], "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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