Involvement of dysregulated RNA binding protein and alternative splicing regulatory networks in diabetic nephropathy from type 2 albuminuric cohorts.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40597902", "kind": "science-record", "revision": 2, "content_hash": "sha256:81c4a2d9efa329cf607ed72e9bd87dbfc7f241528c168afe0d5c74f0d0cb0c16", "created_at": "2026-11-01T20:30:41Z", "updated_at": "2026-11-01T21:35:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Involvement of dysregulated RNA binding protein and alternative splicing regulatory networks in diabetic nephropathy from type 2 albuminuric cohorts.", "doi": "10.1186/s12882-025-04237-6", "pmid": "40597902", "authors": ["Yu Wang", "Jingjing Zhang", "Qian Tang"], "journal": "BMC nephrology", "year": 2025, "abstract": "BACKGROUND: Diabetic nephropathy (DN) is a primary contributor to end-stage renal disease, yet the underlying molecular mechanisms remain incompletely understood. This study aims to elucidate the role of RNA-binding proteins (RBPs) and RBP-alternative splicing (AS) regulatory networks in the pathogenesis of DN.\nMETHODS: Two RNA-seq datasets (GSE117085 and GSE142025) were retrieved from the Sequence Read Archive (SRA) database. Regulated alternative splicing events (RASEs) and genes (RASGs) of RASEs, along with differentiated RBPs, were identified. Validated differentiated RBPs were correlated with clinical features using the Nephroseq v5 online platform. Using the DN mouse model and RT-qPCR, validated the alternative splicing of RNA.\nRESULTS: Our analysis revealed 15 differentiated RBP genes and 423 RASEs in the kidney cortex of DN rats compared to controls. Enrichment analysis highlighted lipid metabolism pathways for RASGs. Seven of the identified RBPs were validated in kidney biopsy samples from DN patients versus controls. A co-deregulatory network was constructed based on dysregulated RBPs and RASEs, with select RASGs identified. In vivo experiments, compared to normal mice, the mRNA levels of RPS19 were significantly elevated in the renal tissues of DN mice, while the levels of CPEB4 and CRYZ were markedly decreased.\nCONCLUSION: In conclusion, this study provides evidence implicating dysregulated RBPs and RBP-AS regulatory networks in the development of diabetic nephropathy. The validated RBPs exhibited close associations with clinical biomarkers, reinforcing their potential as therapeutic targets for DN. These findings enhance our understanding of the molecular basis of DN and offer new insights for future research and intervention strategies.\nCLINICAL TRIAL: Not applicable.", "claims": [{"id": "claim-method", "statement": "Therefore, the Spearman correlation for each differentially expressed RBP and RASE pair was calculated, and a dysregulation network was created (Fig. 3D).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40597902", "locator": "sections[13] \"Differentially expressed RBPs are co-expressed with the alternative splicing genes\" paragraph 2", "quote": "Therefore, the Spearman correlation for each differentially expressed RBP and RASE pair was calculated, and a dysregulation network was created (Fig. 3D)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "SRA database (https://catalog.data.gov/dataset/sequence-read-archive-sra, accession number: SRP153385 and SRP237545. All data generated or analyzed during this study are included in this published article [and its supplementary information files].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40597902", "locator": "sections[24] \"notes\" paragraph 1", "quote": "SRA database (https://catalog.data.gov/dataset/sequence-read-archive-sra, accession number: SRP153385 and SRP237545. All data generated or analyzed during this study are included in this published article [and its supplementary information files]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our analysis revealed 15 differentiated RBP genes and 423 RASEs in the kidney cortex of DN rats compared to controls.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40597902", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Our analysis revealed 15 differentiated RBP genes and 423 RASEs in the kidney cortex of DN rats compared to controls."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Our analysis revealed 15 differentiated RBP genes and 423 RASEs in the kidney cortex of DN rats compared to controls.", "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:40597902"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R4", "reachable": false, "accessions": ["SRP153385 and SRP237545"], "resolved_accessions": [], "statements": ["SRA database (https://catalog.data.gov/dataset/sequence-read-archive-sra, accession number: SRP153385 and SRP237545. All data generated or analyzed during this study are included in this published article [and its supplementary information files]."], "basis": "The paper names SRP153385 and SRP237545, but the accession does not resolve in the repository (no reason recorded), so the data cannot be reached from here. 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METHODS: Two RNA-seq datasets (GSE117085 and GSE142025) were retr", "terial. Supplementary Material 1: Figure S1. Transcriptome analysis of DEGs in diabetic rat kidney cort"], "order_basis": "paper_text_order:431", "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": ["e Nephroseq v5 online platform. Using the DN mouse model and RT-qPCR, validated the alternative splic", "BPs and RASEs, with select RASGs identified. In vivo experiments, compared to normal mice, the mR", "e Nephroseq v5 online platform. Using the DN mouse model and RT-qPCR, validated the alternative", "nes and 423 RASEs in the kidney cortex of DN rats compared to controls. Enrichment analysis hi"], "order_basis": "paper_text_order:781", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nline platform. Using the DN mouse model and RT-qPCR, validated the alternative splicing of RNA.", "ne platform. Using the DN mouse model and RT-qPCR, validated the alternative splicing of RNA.", "Mix II (VAZYME). Quantitative real-time PCR (RT-qPCR) was subsequently performed using the AceQ q", "II (VAZYME). Quantitative real-time PCR (RT-qPCR) was subsequently performed using the AceQ q"], "order_basis": "paper_text_order:797", "id": "assay:3"}, {"role": "analysis", "definition_id": "correlation_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["spearman_rho"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Therefore, the Spearman correlation for each differentially expressed RBP and RASE pair was calculated, and a dysregulation network was created (Fig. 3D)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}