GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37622120", "kind": "science-record", "revision": 4, "content_hash": "sha256:02efd22fe0a702b95420454f22316b9935d61a87b1a8f9ad73bc31da42272c3e", "created_at": "2026-11-01T19:02:24Z", "updated_at": "2026-11-01T22:52:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy.", "doi": "10.3389/fimmu.2023.1127612", "pmid": "37622120", "authors": ["Xiaohui Li", "Jialu Liu", "Mengru Zeng", "Kexin Yang", "Shumin Zhang", "Yifei Liu", "Xiangxiang Yin", "Chanyue Zhao", "Wenpeng Wang", "Li Xiao"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: Diabetic nephropathy (DN) is one of the most common diabetic complications, which has become the primary cause of end-stage renal disease (ESRD) globally. Macrophage infiltration has been proven vital in the occurrence and development of DN. This study was designed to investigate the hub genes involved in macrophage-mediated inflammation of DN via bioinformatics analysis and experimental validation.\nMethods: Gene microarray datasets were obtained from the Gene Expression Omnibus (GEO) public website. Integrating the CIBERSORT, weighted gene co-expression network analysis (WGCNA) and DEGs, we screened macrophage M1-associated key genes with the highest intramodular connectivity. Subsequently, the Least Absolute Shrinkage and Selection Operator (LASSO) regression was utilized to further mine hub genes. GSE104954 acted as an external validation to predict the expression levels and diagnostic performance of these hub genes. The Nephroseq online platform was employed to evaluate the clinical implications of these hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to elucidate the dominant biological functions and signal pathways. Finally, we conducted experiments to verify the role of GBP2 in M1 macrophage-mediated inflammatory response and the underlying mechanism of this role.\nResults: Sixteen DEGs with the highest connectivity in M1 macrophages-associated module (paleturquoise module) were determined. Subsequently, we identified four hub genes through LASSO regression analysis, including CASP1, MS4A4A, CD53, and GBP2. Consistent with the training set, expression levels of these four hub genes manifested memorably elevated and the ROC curves indicated a good diagnostic accuracy with an area under the curve of greater than 0.8. Clinically, enhanced expression of these four hub genes predicted worse outcomes of DN patients. Given the known correlation between the first three hub genes and macrophage-mediated inflammation, experiments were performed to demonstrate the effect of GBP2, which proved that GBP2 contributed to M1 polarization of macrophages by activating the notch1 signaling pathway.\nConclusion: Our findings detected four hub genes, namely CASP1, MS4A4A, CD53, and GBP2, may involve in the progression of DN via pro-inflammatory M1 macrophage phenotype. GBP2 could be a promising prognostic biomarker and intervention target for DN by regulating M1 polarization.", "claims": [{"id": "claim-method", "statement": "The limma R package was employed to determine DEGs by the criteria of |logFC (fold change) | > 1 and adjusted p< 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37622120", "locator": "sections[4] \"Data preprocessing and sscreening of DEGs\" paragraph 2", "quote": "The limma R package was employed to determine DEGs by the criteria of |logFC (fold change) | > 1 and adjusted p< 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37622120", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified four M1 macrophage-associated hub genes in diabetic nephropathy and demonstrated that GBP2 promotes M1 polarization by activating the Notch1 signaling pathway.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37622120", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our findings detected four hub genes, namely CASP1, MS4A4A, CD53, and GBP2, may involve in the progression of DN via pro-inflammatory M1 macrophage phenotype."}, {"asset": "source:pmid:37622120", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "GBP2 could be a promising prognostic biomarker and intervention target for DN by regulating M1 polarization."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified four M1 macrophage-associated hub genes in diabetic nephropathy and demonstrated that GBP2 promotes M1 polarization by activating the Notch1 signaling pathway.", "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:37622120"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE104954"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE104954"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37622120", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2023.1127612", "sha256": "sha256:6ccdad982fb3243d96920d69e3523daa6686b2cb8f86ebd01c5f56f3853f72e4", "bytes": 42260, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2023.1127612", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10445759", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE104954", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE104954", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE104954", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Materials. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37622120", "data:geo:GSE104954"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE104954"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:51:22Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11003, "completion_tokens": 1938, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37622120", "type": "paper", "label": "pmid:37622120"}, {"id": "source:pmid:37622120", "type": "manuscript", "label": "PMID 37622120 full text"}, {"id": "data:geo:GSE104954", "type": "dataset", "label": "GEO GSE104954"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37622120", "type": "paper", "label": "pmid:37622120"}, {"id": "source:pmid:37622120", "type": "manuscript", "label": "PMID 37622120 full text"}, {"id": "data:geo:GSE104954", "type": "dataset", "label": "GEO GSE104954"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37622120", "type": "extraction", "used": ["source:pmid:37622120"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE104954", "type": "accession_resolution", "used": ["data:geo:GSE104954"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:37622120", "parent_hash": "sha256:1715b46e4c95b5828c87b9c89ed6a1f504489b86dae2190f032cfeb05b13503a", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE104954 licence not read", "asset:data:geo:GSE104954 not downloaded", "asset:data:geo:GSE30122 licence not read", "asset:data:geo:GSE30122 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["s and experimental validation. 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