Impdh1 was identified as a key protein promotes diabetic vasculopathy by intervention of vascular endothelial cell pyroptosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40082765", "kind": "science-record", "revision": 4, "content_hash": "sha256:7a171e03b53b86d24022b2df951bdca4989e572262fd8ae37ef73103e9c4f098", "created_at": "2026-11-01T20:30:18Z", "updated_at": "2026-11-01T22:56:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Impdh1 was identified as a key protein promotes diabetic vasculopathy by intervention of vascular endothelial cell pyroptosis.", "doi": "10.1186/s12872-025-04604-z", "pmid": "40082765", "authors": ["Ruiqiang Xie", "Hong Gao", "Hongyan Xie", "Chunguang Xie", "Tianhao Li"], "journal": "BMC cardiovascular disorders", "year": 2025, "abstract": "BACKGROUND: Diabetic angiopathy (DA) is a diabetic vascular complication. Pyroptosis is an inflammatory death that plays an important role in the development of DA, but the underlying mechanisms have not been fully elucidated.\nMETHODS: The GSE169332 dataset from the Gene Expression Omnibus (GEO) was subjected to single-cell RNA sequencing (scRNA-seq) analysis, and the data of diabetic mice were subjected to bulk RNA-seq. The pathway through which the inflammatory microenvironment participated in the DA was explored by pseudotime analysis and cell-cell communication. DA models were constructed using in vitro mouse models. The histopathological changes in the collected aorta were observed by hematoxylin and eosin (H&E) and Masson staining. The distribution and expression of the phenotypic markers related to pyroptosis in aortic tissues (NLRP3, pro-Caspase1, and GSDMD-N) were observed by immunohistochemistry (IHC) or immunofluorescence (IF) staining. Following the silencing of the expression of high glucose (HG)-induced Impdh1 in endothelial cells (ECs), Impdh1 expression was detected by real-time quantitative reverse transcription PCR (qRT-PCR), and the expression of Impdh1, NLRP3, pro-Caspase1, and GSDMD was detected by IF staining; cell migration was detected by cell scratch assay, cell viability was detected by cell counting kit-8 (CCK-8) assay, and tube formation was detected by tube formation assay; the levels of IL-1β and IL-18 were detected using the enzyme-linked immunosorbent assay (ELISA) kits.\nRESULTS: Impdh1 was identified by scRNA-seq and bulk RNA-seq as a key molecule in the progression of DA associated with pyroptosis of aortic ECs. By constructing mouse models of DA, it was found that silencing Impdh1 can inhibit mouse aortic pyroptosis. Silencing of the expression of HG-induced Impdh1 revealed an effective amelioration of EC damage and pyroptosis.\nCONCLUSION: Impdh1 is identified as a potential pyroptosis-related gene associated with DA by scRNA-seq of GEO data and bulk RNA-seq. Impdh1 protects aortic ECs by inhibiting pyroptosis and inflammation.\nCLINICAL TRIAL NUMBER: Not applicable.", "claims": [{"id": "claim-method", "statement": "Differential expression analysis of genes was performed using DESeq2 to screen for DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40082765", "locator": "sections[16] \"Bulk RNA-seq\" paragraph 3", "quote": "Differential expression analysis of genes was performed using DESeq2 to screen for DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40082765", "locator": "sections[28] \"Data availability\" paragraph 2", "quote": "The datasets generated during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Impdh1 was significantly up-regulated in diabetic mice.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40082765", "locator": "sections[23] \"Identification of DEGs by bulk RNA-seq and functional enrichment analyses of the DEGs\" paragraph 2", "quote": "A total of 250 DEGs were obtained by bulk RNA-seq analysis, including 141 up-regulated and 109 down-regulated genes, and Impdh1 was significantly up-regulated in diabetic mice (Fig. 5A-B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Impdh1 was significantly up-regulated in diabetic mice.", "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:40082765"], "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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RESULTS: Impdh1 was identified by scRNA-seq and bulk RNA-seq as a key molecule in the pr", "yroptosis-related gene associated with DA by scRNA-seq of GEO data and bulk RNA-seq. Impdh1 protect"], "order_basis": "paper_text_order:396", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["data of diabetic mice were subjected to bulk RNA-seq. The pathway through which the inflammatory", "Impdh1 was identified by scRNA-seq and bulk RNA-seq as a key molecule in the progression of DA a", "ed with DA by scRNA-seq of GEO data and bulk RNA-seq. Impdh1 protects aortic ECs by inhibiting py", "n Omnibus (GEO) was subjected to single-cell RNA sequencing (scRNA-seq) analysis, and the data of diabet"], "order_basis": "paper_text_order:408", "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": 0.99, "evidence": ["cRNA-seq) analysis, and the data of diabetic mice were subjected to bulk RNA-seq. The pathway throu", "n. DA models were constructed using in vitro mouse models. The histopathological changes in the", "th pyroptosis of aortic ECs. By constructing mouse models of DA, it was found that silencing Im", "was found that silencing Impdh1 can inhibit mouse aortic pyroptosis. Silencing of the expressi"], "order_basis": "paper_text_order:470", "id": "assay:3"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["pro-Caspase1, and GSDMD-N) were observed by immunohistochemistry (IHC) or immunofluorescence (IF) staining. F", "re observed by immunohistochemistry (IHC) or immunofluorescence (IF) staining. Following the silencing of th", "MD-N) were observed by immunohistochemistry (IHC) or immunofluorescence (IF) staining. Follow"], "order_basis": "paper_text_order:981", "id": "assay:4"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["Impdh1 expression was detected by real-time quantitative reverse transcription PCR (qRT-PCR), and the expression of Impdh1, NLR"], "order_basis": "paper_text_order:1195", "id": "assay:5"}, {"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": ["ability was detected by cell counting kit-8 (CCK-8) assay, and tube formation was detected by t"], "order_basis": "paper_text_order:1437", "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": ["using the enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Impdh1 was identified by scR", "s of IL-1β and IL-18 were detected using the enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Impdh1 was identified"], "order_basis": "paper_text_order:1562", "id": "assay:7"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["al cells (HUVECs) (CBP60340, ATCC, USA) were cultured in vitro and randomly assigned to the NG group"], "order_basis": "paper_text_order:3314", "id": "assay:8"}, {"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": ["noculated into 6-well plates for 24 h before transfection. When cell confluence reached about 50%, the", "When cell confluence reached about 50%, the transfection reagent and plasmids or vector complexes (20", "g to the protocols of the Lipofectamine 3000 Transfection Kit (11668-027, Invitrogen, USA) and mixed f", "t (11668-027, Invitrogen, USA) and mixed for transfection. After 6 h of transfection, the culture medi"], "order_basis": "paper_text_order:3440", "id": "assay:9"}, {"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": ["Differential expression analysis of genes was performed using DESeq2 to screen for DEGs."], "order_basis": "consumes_earlier_output", "id": "assay:10"}]}