VEGFA promotes the occurrence of PLA2R-associated idiopathic membranous nephropathy by angiogenesis via the PI3K/AKT signalling pathway.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36114523", "kind": "science-record", "revision": 5, "content_hash": "sha256:234319fa7603e003f1f928e709c8641af91d76ee97766cd38f2344f46e03d5b0", "created_at": "2026-11-01T18:15:22Z", "updated_at": "2026-11-01T22:50:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "VEGFA promotes the occurrence of PLA2R-associated idiopathic membranous nephropathy by angiogenesis via the PI3K/AKT signalling pathway.", "doi": "10.1186/s12882-022-02936-y", "pmid": "36114523", "authors": ["Ben Ke", "Jinjing Huang", "Zhibing Duan", "Wen Shen", "Yao Wu", "Weiping Tu", "Xiangdong Fang"], "journal": "BMC nephrology", "year": 2022, "abstract": "BACKGROUND: The M-type phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) is a common immune-related disease in adults. Vascular endothelial growth factor A (VEGFA) is the key mediator of angiogenesis, which leads to numerous kidney diseases. However, the role of VEGFA in IMN is poorly understood.\nMETHODS: In the present study, we downloaded the microarray data GSE115857 from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified with R software. The cytoHubba plug-in were used to identify hub genes from the protein-protein interaction network. Gene set enrichment analysis (GSEA) was used to identify signalling pathway in IMN. CCK8 was performed to assess the cell viability in human vascular endothelial cells (HVECs). Then, passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Animals treated with VEGFA inhibitor bevacizumab (BV), with saline as a positive control. Proteinuria was evaluated by biochemical measurements. Immunohistochemistry and immunofluorescence was used to evaluate relative proteins expression. Electron microscopy was performed to observe the thickness of the glomerular basement membrane (GBM).\nRESULTS: We revealed 3 hub genes, including one up-regulated gene VEGFA and two down-regulated genes JUN and FOS, which are closely related to the development of PLA2R-associated IMN. Pathway enrichment analysis found that the biological process induced by VEGFA is associated with PI3K/Akt signalling. GSEA showed that the signalling pathway of DEGs in GSE115857 was focused on angiogenesis, in which VEGFA acts as a core gene. We confirmed the high expression of VEGFA, PI3K, and AKT in IMN renal biopsy samples with immunohistochemistry. In HVECs, we found that BV suppresses cell viability in a time and dose dependent manner. In vivo, we found low dose of BV attenuates proteinuria via inhibiting VEGFA/PI3K/AKT signalling. Meanwhile, low dose of BV alleviates the thickening of the GBM.\nCONCLUSION: VEGFA/PI3K/AKT signalling may play significant roles in the pathogenesis of IMN, which may provide new targets for the treatment of IMN.", "claims": [{"id": "claim-method", "statement": "The limma package in R software (Version 3.6.2) was utilized to screen differentially expressed genes (DEGs) between the IMN group and living donor group. An adjusted p value of < 0.05 and |logFC|> 1.0 were considered statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36114523", "locator": "sections[5] \"Identification of differentially expressed genes\" paragraph 2", "quote": "The limma package in R software (Version 3.6.2) was utilized to screen differentially expressed genes (DEGs) between the IMN group and living donor group. An adjusted p value of < 0.05 and |logFC|> 1.0 were considered statistically significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available in the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/, GSE 115,857) repository.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36114523", "locator": "sections[32] \"notes\" paragraph 1", "quote": "The datasets analysed during the current study are available in the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/, GSE 115,857) repository."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 1422 differentially expressed genes were identified in GSE115857, including 952 up-regulated and 470 down-regulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36114523", "locator": "sections[17] \"Identification of DEGs\" paragraph 2", "quote": "A total of 1422 DEGs were identified in GSE115857, including 952 up-regulated genes and 470 down-regulated genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 1422 differentially expressed genes were identified in GSE115857, including 952 up-regulated and 470 down-regulated genes.", "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:36114523"], "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:GSE115857"], "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:GSE115857"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36114523", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12882-022-02936-y", "sha256": "sha256:adced79ac8c65337cd8459663d12b41e89617335af934aa5f2b9927a10aa4a2c", "bytes": 43319, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12882-022-02936-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9482157", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE115857", "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=GSE115857", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE115857", "version": null, "note": "The datasets analysed during the current study are available in the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/, GSE 115,857) repository.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed during the current study are available in the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/, GSE 115,857) repository.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3191893", "GSM3191894", "GSM3191895", "GSM3191896", "GSM3191897", "GSM3191898", "GSM3191899", "GSM3191900", "GSM3191901", "GSM3191902", "GSM3191903", "GSM3191904", "GSM3191905", "GSM3191906", "GSM3191907", "GSM3191908", "GSM3191909", "GSM3191910", "GSM3191911", "GSM3191912", "GSM3191913", "GSM3191914", "GSM3191915", "GSM3191916", "GSM3191917", "GSM3191918", "GSM3191919", "GSM3191920", "GSM3191921", "GSM3191922", "GSM3191923", "GSM3191924", "GSM3191925", "GSM3191926", "GSM3191927", "GSM3191928", "GSM3191929", "GSM3191930", "GSM3191931", "GSM3191932", "GSM3191933", "GSM3191934", "GSM3191935", "GSM3191936", "GSM3191937", "GSM3191938", "GSM3191939", "GSM3191940", "GSM3191941", "GSM3191942", "GSM3191943", "GSM3191944", "GSM3191945", "GSM3191946", "GSM3191947", "GSM3191948", "GSM3191949", "GSM3191950", "GSM3191951", "GSM3191952", "GSM3191953", "GSM3191954", "GSM3191955", "GSM3191956", "GSM3191957", "GSM3191958", "GSM3191959", "GSM3191960", "GSM3191961", "GSM3191962", "GSM3191963", "GSM3191964", "GSM3191965", "GSM3191966", "GSM3191967", "GSM3191968", "GSM3191969", "GSM3191970", "GSM3191971", "GSM3191972", "GSM3191973", "GSM3191974", "GSM3191975", "GSM3191976", "GSM3191977", "GSM3191978"], "sample_count": 86, "group_sizes": null, "group_sizes_basis": null, "platform": "14951", "taxon": "Homo sapiens", "title": "SPECIFIC BIOMARKERS ASSOCIATED WITH CHRONIC RENAL LESIONS IN IGA NEPHROPATHY PATIENTS. A MULTICENTER STUDY", "resolution_checked_at": "2026-11-01T17:30:42Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE115857 not downloaded", "asset:data:geo:GSE115857 licence not read"]}, "analysis": {"state": "partial", "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 limma package in R software (Version 3.6.2) was utilized to screen differentially expressed genes (DEGs) between the IMN group and living donor group. 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CCK8 was performed to assess the cell viability i"], "order_basis": "paper_text_order:796", "id": "assay:1"}, {"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": ["ability in a time and dose dependent manner. In vivo, we found low dose of BV attenuates proteinu", "passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A", "ssive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A", "f Nanchang University (Nanchang, China). All rats were housed under standard specific pathogen-free"], "order_basis": "paper_text_order:939", "id": "assay:2"}, {"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": ["a was evaluated by biochemical measurements. Immunohistochemistry and immunofluorescence was used to evaluate", "3K, and AKT in IMN renal biopsy samples with immunohistochemistry. In HVECs, we found that BV suppresses cell", "mical measurements. Immunohistochemistry and immunofluorescence was used to evaluate relative proteins expre"], "order_basis": "paper_text_order:1147", "id": "assay:3"}, {"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 limma package in R software (Version 3.6.2) was utilized to screen differentially expressed genes (DEGs) between the IMN group and living donor group. An adjusted p value of < 0.05 and |logFC|> 1.0 were considered statistically significant."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}