Role and mechanism of IRF9 in promoting the progression of rheumatoid arthritis by regulating macrophage polarization via PSMA5.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39170377", "kind": "science-record", "revision": 4, "content_hash": "sha256:07b93a093895c64cf2a05bd627d171806a609ad6f85acc7461f742c204f87f1f", "created_at": "2026-11-01T20:29:18Z", "updated_at": "2026-11-01T22:55:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Role and mechanism of IRF9 in promoting the progression of rheumatoid arthritis by regulating macrophage polarization via PSMA5.", "doi": "10.1016/j.heliyon.2024.e35589", "pmid": "39170377", "authors": ["Yue Guan", "Xin Li", "Hemin Yang", "Siyu Xu", "Lidong Shi", "Yangyang Liu", "Lingdan Kong", "Ying Qin"], "journal": "Heliyon", "year": 2024, "abstract": "Aim: To explore the mechanisms of IRF9 in the progression of rheumatoid arthritis(RA), and the effects of IRF9 on M1/M2 polarization.\nMethods: RA dataset (GSE55457) was downloaded from GEO. Correlation analysis between IRF9 and its downstream target protein PSMA5 was performed using bioinformatics analysis. The M1/M2 cell ratio of peripheral blood mononuclear cells which from 20 healthy specimen and 40 RA patients was determined. The expression of IRF9 and PSMA5 was detected using qPCR and Western blot. Then, knockdown IRF9 in RAW264.7 cell line (sh-IRF9 RAW264.7) was constructed. The effect of sh-IRF9 RAW264.7 on RA was explored by constructing a CIA mouse model.\nResults: IRF9 is upregulated in RA and is of good early screening effect. The results of pathway analysis showed that IRF9 targets and regulates the PSMA5 signaling pathway. IRF9 and PSMA5 were significantly elevated in RA patients, M1/M2 ratio was also increased. The effects of IRF9 on RAW264.7 macrophages were deeply explored in vitro, revealing that knockdown of IRF9 suppressed PSMA5, M1/M2 ratio and the secretion of pro-inflammatory factor in RAW264.7. In mouse in vivo experiments, sh-IRF9 RAW264.7 cells were found to modulate RA by downregulating PSMA5, modulating the M1/M2 ratio through enhancing the anti-inflammatory factor, and suppressing the pro-inflammatory factor.\nConclusion: IRF9 promoted the progression of RA via regulating macrophage polarization through PSMA5.", "claims": [{"id": "claim-method", "statement": "The GSE55457 gene expression matrix was subjected to differential analysis using the R software Limma package, which revealed a statistically significant upregulation of IRF 9 in RA(Fig. 1A, Supplementary Figs. 1A–1B).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39170377", "locator": "sections[18] \"Analysis of RA dataset\" paragraph 2", "quote": "The GSE55457 gene expression matrix was subjected to differential analysis using the R software Limma package, which revealed a statistically significant upregulation of IRF 9 in RA(Fig. 1A, Supplementary Figs. 1A–1B)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All experimental data included in this study can be obtained by contacting the first author if needed.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39170377", "locator": "sections[24] \"Availability of data and materials\" paragraph 2", "quote": "All experimental data included in this study can be obtained by contacting the first author if needed."}], "state": "complete"}, {"id": "claim-target-result", "statement": "IRF9 had perfect early-screening performance for rheumatoid arthritis in the GSE55457 dataset, with an ROC value of 1.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39170377", "locator": "sections[18] \"Analysis of RA dataset\" paragraph 2", "quote": "The efficacy of IRF 9 in early screening for RA was assessed by constructing the ROC curve, which yielded a perfect ROC = 1, indicating the crucial role of IRF 9 in identifying RA at an early stage(Fig. 1B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "IRF9 had perfect early-screening performance for rheumatoid arthritis in the GSE55457 dataset, with an ROC value of 1.", "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:39170377"], "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:GSE55457"], "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:GSE55457"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39170377", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2024.e35589", "sha256": "sha256:6a3271792aadd3d9c09cd47262ea8b4e9af95212d15a0f4abd64d9c994fc6c4e", "bytes": 45500, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2024.e35589", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11336755", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE55457", "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=GSE55457", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55457", "version": null, "note": "All experimental data included in this study can be obtained by contacting the first author if needed.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All experimental data included in this study can be obtained by contacting the first author if needed.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1337304", "GSM1337305", "GSM1337306", "GSM1337307", "GSM1337308", "GSM1337309", "GSM1337310", "GSM1337311", "GSM1337312", "GSM1337313", "GSM1337314", "GSM1337315", "GSM1337316", "GSM1337317", "GSM1337318", "GSM1337319", "GSM1337320", "GSM1337321", "GSM1337322", "GSM1337323", "GSM1337324", "GSM1337325", "GSM1337326", "GSM1337327", "GSM1337328", "GSM1337329", "GSM1337330", "GSM1337331", "GSM1337332", "GSM1337333", "GSM1337334", "GSM1337335", "GSM1337336"], "sample_count": 33, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation [Jena]", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE55457 not downloaded", "asset:data:geo:GSE55457 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The GSE55457 gene expression matrix was subjected to differential analysis using the R software Limma package, which revealed a statistically significant upregulation of IRF 9 in RA(Fig. 1A, Supplementary Figs. 1A–1B)."}}, {"id": "method-2", "family": "regression_modelling", "specific": "ols", "label": "Regression modelling", "dsl_operations": ["ols_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.8, "band": "high", "quote": "Linear regression"}}, {"id": "method-3", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE55457"], "resolved_accessions": ["GSE55457"], "statements": ["All experimental data included in this study can be obtained by contacting the first author if needed."], "basis": "The paper names GSE55457 in GEO and the accession resolves in the repository. 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Then, knockdown IRF9 in RA", "M1/M2 cell ratio in PBMC of RA patients. B. qPCR for the expression of IRF9 and PSMA5 in PBMC"], "order_basis": "paper_text_order:570", "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": ["f IRF9 and PSMA5 was detected using qPCR and Western blot. Then, knockdown IRF9 in RAW264.7 cell line", "the expression of IRF9 and PSMA5 in PBMC. C. Western blot for the protein expression level of IRF9 and"], "order_basis": "paper_text_order:579", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["detected using qPCR and Western blot. Then, knockdown IRF9 in RAW264.7 cell line (sh-IRF9 RAW264.7", "ere deeply explored in vitro, revealing that knockdown of IRF9 suppressed PSMA5, M1/M2 ratio and th", "on was conducted. In the sh-IRF9 group, IRF9 shRNA (2 mg/kg) was injected intravenously into th"], "order_basis": "paper_text_order:600", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["4.7 on RA was explored by constructing a CIA mouse model. Results: IRF9 is upregulated in RA and is o", "ro-inflammatory factor in RAW264.7. In mouse in vivo experiments, sh-IRF9 RAW264.7 cells were fou", "4.7 on RA was explored by constructing a CIA mouse model. Results: IRF9 is upregulated in RA an", "n of pro-inflammatory factor in RAW264.7. In mouse in vivo experiments, sh-IRF9 RAW264.7 cells"], "order_basis": "paper_text_order:744", "id": "assay:4"}, {"role": "data_generation", "definition_id": "clinical_cohort", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["hort of 40 RA patients and obtained 20 whole blood samples from healthy individuals who underwent medical ch"], "order_basis": "paper_text_order:1644", "id": "assay:5"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["eckups at our hospital for this study. Using flow cytometry, we conducted an analysis on the polarizatio"], "order_basis": "paper_text_order:7104", "id": "assay:6"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["pression level of IRF9 and PSMA5 in PBMC. D. ELISA for the expression of TGF-β and IL-10 in ser", "e expression of TGF-β and IL-10 in serum. E. ELISA for the expression of TNF-α, IL-1β in serum."], "order_basis": "paper_text_order:7996", "id": "assay:7"}, {"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 GSE55457 gene expression matrix was subjected to differential analysis using the R software Limma package, which revealed a statistically significant upregulation of IRF 9 in RA(Fig. 1A, Supplementary Figs. 1A–1B)."], "order_basis": "consumes_earlier_output", "id": "assay:8"}]}