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pmid:38161356
APOL1 Induces Pyroptosis of Fibroblasts Through NLRP3/Caspase-1/GSDMD Signaling Pathway in Ulcerative Colitis.
Fangqing Zhu · Sheng Li · Qiuping Gu · Ningsheng Xie · Yinxia Wu
Journal of inflammation research · 2023 doi:10.2147/JIR.S437875
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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However, at present, it is not clear whether pyroptosis of colonic fibroblasts is involved in the pathogenesis and progression of UC.\nMethods: In this study, key genes associated with UC were identified by bioinformatics analysis. Datasets were downloaded from the Gene Expression Omnibus (GEO) database (GSE193677). The differentially expressed genes were analyzed, and the hub genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed genes. We also downloaded the dataset from GEO for single-cell RNA sequencing (GSE231993). The expression of key genes was verified by immunohistochemistry, immunofluorescence and Western blot, and the specific pathways of key genes inducing pyroptosis in cell lines were explored.\nResults: The results of bioinformatics analysis showed that the expression of APOL1 and CXCL1 in UC tissues was significantly higher than that in normal tissues. The results of single-cell analysis showed that the two genes were co-localized to fibroblasts. These results were consistent with the results of immunohistochemistry and immunofluorescence colocalization in human intestinal mucosa specimens. Furthermore, APOL1 overexpression induced NLRP3-caspase1-GSDMD-mediated pyroptosis of fibroblasts, which was confirmed by Western blot.\nConclusion: APOL1 induces pyroptosis of fibroblasts mediated by NLRP3-Caspase1-GSDMD signaling pathway and promote the release of chemokines CXCL1. Fibroblasts may play a crucial role in the pathogenesis and progression of UC.", "claims": [{"id": "claim-method", "statement": "One-way analysis of variance (ANOVA) was used, as appropriate, to determine significant differences between groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38161356", "locator": "sections[11] \"Statistical Analysis\" paragraph 2", "quote": "One-way analysis of variance (ANOVA) was used, as appropriate, to determine significant differences between groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We obtained the GSE193677 dataset from the GEO database. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE193677"], "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:GSE193677"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38161356", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/JIR.S437875", "sha256": "sha256:caa8fa6233b892001134c41e65bc46ee9dcf7f91b129f0c67282cd67fc6a5da1", "bytes": 38129, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/JIR.S437875", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10757784", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE193677", "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=GSE193677", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE193677", "version": null, "note": "We obtained the GSE193677 dataset from the GEO database. 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"GSM5978963", "GSM5978964", "GSM5978965", "GSM5978966", "GSM5978967", "GSM5978968", "GSM5978969", "GSM5978970", "GSM5978971", "GSM5978972", "GSM5978973", "GSM5978974", "GSM5978975", "GSM5978976", "GSM5978977", "GSM5978978", "GSM5978979", "GSM5978980", "GSM5978981", "GSM5978982", "GSM5978983", "GSM5978984", "GSM5978985", "GSM5978986", "GSM5978987", "GSM5978988"], "sample_count": 2490, "group_sizes": null, "group_sizes_basis": null, "platform": "16791", "taxon": "Homo sapiens", "title": "Biopsy expression profiling of an adult inflammatory bowel disease cohort", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE231993", "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=GSE231993", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE231993", "version": null, "note": "We obtained the GSE193677 dataset from the GEO database. Colon biopsy specimens obtained from non-inflammatory controls and from individuals diagnosed with UC within the GSE193677 dataset were selected for data analysis using weighted gene co-expression network analysis(WGCNA).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "We obtained the GSE193677 dataset from the GEO database. Colon biopsy specimens obtained from non-inflammatory controls and from individuals diagnosed with UC within the GSE193677 dataset were selected for data analysis using weighted gene co-expression network analysis(WGCNA).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM7307094", "GSM7307095", "GSM7307096", "GSM7307097", "GSM7307098", "GSM7307099", "GSM7307100", "GSM7307101", "GSM7307102", "GSM7307103", "GSM7307104", "GSM7307105"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "18573", "taxon": "Homo sapiens", "title": "Selective oxidative protection leads to tissue topological changes orchestrated by macrophage during ulcerative colitis", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE193677 not downloaded", "asset:data:geo:GSE193677 licence not read", "asset:data:geo:GSE231993 not downloaded", "asset:data:geo:GSE231993 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "One-way analysis of variance (ANOVA) was used, as appropriate, to determine significant differences between groups."}}, {"id": "method-2", "family": "image_quantification", "specific": "densitometry", "label": "Image analysis / quantification", "dsl_operations": ["segment_objects", "quantify_intensity"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["image_stack"], "evidence": {"score": 0.8, "band": "high", "quote": "optical density"}}], "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": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: anova."}, "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": ["GSE193677", "GSE231993"], "resolved_accessions": ["GSE193677", "GSE231993"], "statements": ["We obtained the GSE193677 dataset from the GEO database. Colon biopsy specimens obtained from non-inflammatory controls and from individuals diagnosed with UC within the GSE193677 dataset were selected for data analysis using weighted gene co-expression network analysis(WGCNA)."], "basis": "The paper names GSE193677, GSE231993 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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