Endoplasmic Reticulum Stress Mediates Renal Tubular Vacuolation in BK Polyomavirus-Associated Nephropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35464062", "kind": "science-record", "revision": 5, "content_hash": "sha256:f1b9cdc0c89cd6077a4576bb46cf1e620446f508952e527501e6c94bdb70a264", "created_at": "2026-11-01T18:14:19Z", "updated_at": "2026-11-01T22:48:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Endoplasmic Reticulum Stress Mediates Renal Tubular Vacuolation in BK Polyomavirus-Associated Nephropathy.", "doi": "10.3389/fendo.2022.834187", "pmid": "35464062", "authors": ["Guo-Dong Zhao", "Rong Gao", "Xiao-Tao Hou", "Hui Zhang", "Xu-Tao Chen", "Jin-Quan Luo", "Hui-Fei Yang", "Tong Chen", "Xue Shen", "Shi-Cong Yang", "Cheng-Lin Wu", "Gang Huang"], "journal": "Frontiers in endocrinology", "year": 2022, "abstract": "Objective: This study aimed to explore the molecular mechanism of cytoplasmic vacuolation caused by BK polyomavirus (BKPyV) and thus search for potential target for drug repurposing.\nMethods: Morphological features of BK polyomavirus-associated nephropathy (BKPyVAN) were studied under light and electron microscopes. Microarray datasets GSE75693, GSE47199, and GSE72925 were integrated by ComBat, and differentially expressed genes (DEGs) were analyzed using limma. Furthermore, the endoplasmic reticulum (ER)-related genes obtained from GenCLiP 2.0 were intersected with DEGs. GO and KEGG enrichment pathways were performed with intersection genes by R package clusterProfiler. The single-cell RNA sequencing (scRNA-seq) from a BKPyVAN recipient was analyzed with a dataset (GSE140989) downloaded from Gene Expression Omnibus (GEO) as control for gene set variation analysis (GSVA). Immunohistochemistry and electron microscopy of kidney sections from drug-induced ERS mouse models were performed to explore the association of ERS and renal tubular vacuolation. Protein-protein interaction (PPI) network of the intersection genes was constructed to identify hub target. AutoDock was used to screen Food and Drug Administration (FDA)-approved drugs that potentially targeted hub gene.\nResults: Light and electron microscopes exhibited obvious intranuclear inclusions, vacuoles, and virus particles in BKPyV-infected renal tubular cells. Transcriptome analysis revealed 629 DEGs between samples of BKPyVAN and stable transplanted kidneys, of which 16 were ER-associated genes. GO analysis with the intersection genes illustrated that ERS-related pathways were significantly involved, and KEGG analysis showed a prominent enrichment of MAPK, Toll-like receptor, and chemokine signaling pathways. GSVA analysis of the proximal tubule revealed similar pathways enrichment. An electron microscope image of the kidney from ERS mouse models showed an obvious renal tubular vacuolation with prominent activation of ERS markers verified by immunohistochemistry. Furthermore, DDIT3 was identified as the hub gene based on PPI analysis, and ZINCOOOOO1531009 (Risedronate) was indicated to be a potential drug for DDIT3.\nConclusion: ERS was involved in renal tubular cytoplasmic vacuolation in BKPyVAN recipients. Risedronate was screened as a potential drug for BKPyVAN by targeting DDIT3.", "claims": [{"id": "claim-method", "statement": "R package Combat was used to eliminate batch effects. The differentially expressed genes (DEGs) of BKPyVAN and stable transplanted kidneys were analyzed by R package limma. p-Value < 0.05 and | fold change (FC)| > 1.5 were considered statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35464062", "locator": "sections[6] \"Data of Bulk RNA Sequence\" paragraph 2", "quote": "R package Combat was used to eliminate batch effects. The differentially expressed genes (DEGs) of BKPyVAN and stable transplanted kidneys were analyzed by R package limma. p-Value < 0.05 and | fold change (FC)| > 1.5 were considered statistically significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35464062", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Transcriptome analysis revealed 629 DEGs between samples of BKPyVAN and stable transplanted kidneys, of which 16 were ER-associated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35464062", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Transcriptome analysis revealed 629 DEGs between samples of BKPyVAN and stable transplanted kidneys, of which 16 were ER-associated genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Transcriptome analysis revealed 629 DEGs between samples of BKPyVAN and stable transplanted kidneys, of which 16 were ER-associated 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:35464062"], "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:GSE140989"], "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:GSE140989"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35464062", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fendo.2022.834187", "sha256": "sha256:fe24eb70fe1f32e87c2815cb2184f1873d8556cb987b1ee96210a14584169f6e", "bytes": 44797, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fendo.2022.834187", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9027570", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE140989", "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=GSE140989", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE140989", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . 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The differentially expressed genes (DEGs) of BKPyVAN and stable transplanted kidneys were analyzed by R package limma. p-Value < 0.05 and | fold change (FC)| > 1.5 were considered statistically significant."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Protein-protein interaction"}}], "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. 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Microarray datasets GSE75693, GSE47199, and GSE72925 we"], "order_basis": "paper_text_order:380", "id": "assay:1"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tion genes by R package clusterProfiler. The single-cell RNA sequencing (scRNA-seq) from a BKPyVAN recipient was ana", "terProfiler. The single-cell RNA sequencing (scRNA-seq) from a BKPyVAN recipient was analyzed with", "N recipient 5) was processed to generate the single-cell RNA sequencing (scRNA-seq) profile. Detailed information ab", "to generate the single-cell RNA sequencing (scRNA-seq) profile. Detailed information about all sam"], "order_basis": "paper_text_order:746", "id": "assay:2"}, {"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": ["y R package clusterProfiler. The single-cell RNA sequencing (scRNA-seq) from a BKPyVAN recipient was ana", "5) was processed to generate the single-cell RNA sequencing (scRNA-seq) profile. Detailed information ab", "icles in BKPyV-infected renal tubular cells. Transcriptome analysis revealed 629 DEGs between samples o"], "order_basis": "paper_text_order:758", "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": ["trol for gene set variation analysis (GSVA). Immunohistochemistry and electron microscopy of kidney sections f", "minent activation of ERS markers verified by immunohistochemistry. Furthermore, DDIT3 was identified as the hu", "col. Pathological diagnosis was confirmed by immunostaining with antibody against SV40 large T-antigen ("], "order_basis": "paper_text_order:947", "id": "assay:4"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["opy of kidney sections from drug-induced ERS mouse models were performed to explore the associa", "tron microscope image of the kidney from ERS mouse models showed an obvious renal tubular vacuo"], "order_basis": "paper_text_order:1033", "id": "assay:5"}, {"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": ["R package Combat was used to eliminate batch effects. The differentially expressed genes (DEGs) of BKPyVAN and stable transplanted kidneys were analyzed by R package limma. p-Value < 0.05 and | fold change (FC)| > 1.5 were considered statistically significant."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}