{"doi":"10.1016/j.celrep.2024.114310","title":"Interferon-γ induces combined pyroptotic angiopathy and APOL1 expression in human kidney disease","abstract":"Elevated interferon (IFN) signaling is associated with kidney diseases including COVID-19, HIV, and apolipoprotein-L1 (APOL1) nephropathy, but whether IFNs directly contribute to nephrotoxicity remains unclear. Using human kidney organoids, primary endothelial cells, and patient samples, we demonstrate that IFN-γ induces pyroptotic angiopathy in combination with APOL1 expression. Single-cell RNA sequencing, immunoblotting, and quantitative fluorescence-based assays reveal that IFN-γ-mediated expression of APOL1 is accompanied by pyroptotic endothelial network degradation in organoids. Pharmacological blockade of IFN-γ signaling inhibits APOL1 expression, prevents upregulation of pyroptosis-associated genes, and rescues vascular networks. Multiomic analyses in patients with COVID-19, proteinuric kidney disease, and collapsing glomerulopathy similarly demonstrate increased IFN signaling and pyroptosis-associated gene expression correlating with accelerated renal disease progression. Our results reveal that IFN-γ signaling simultaneously induces endothelial injury and primes renal cells for pyroptosis, suggesting a combinatorial mechanism for APOL1-mediated collapsing glomerulopathy, which can be targeted therapeutically.","journal":"Cell Reports","year":2024,"id":421124,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":279183,"name":"Ian B. Stanaway","orcid":"0000-0002-0783-0918","position":1,"is_corresponding":false},{"id":1213957,"name":"Fumika Sano","orcid":null,"position":2,"is_corresponding":false},{"id":748211,"name":"Hongxia Fu","orcid":"0000-0002-6893-8260","position":3,"is_corresponding":false},{"id":467486,"name":"Kelly D. Smith","orcid":"0000-0002-2368-4957","position":4,"is_corresponding":false},{"id":356698,"name":"Shreeram Akilesh","orcid":"0000-0003-3152-7991","position":5,"is_corresponding":false},{"id":748152,"name":"Suzie J. Scales","orcid":"0000-0003-2544-0283","position":6,"is_corresponding":false},{"id":817949,"name":"Jamal El Saghir","orcid":"0000-0002-3779-4583","position":7,"is_corresponding":false},{"id":249666,"name":"Pavan K. Bhatraju","orcid":"0000-0002-2606-4366","position":8,"is_corresponding":false},{"id":467483,"name":"Esther Liu","orcid":"0000-0002-8275-1224","position":9,"is_corresponding":false},{"id":1213958,"name":"Johnson Yang","orcid":null,"position":10,"is_corresponding":false},{"id":467487,"name":"Jennie Lin","orcid":"0000-0002-9328-6700","position":11,"is_corresponding":false},{"id":5959,"name":"Sean Eddy","orcid":"0000-0001-8578-3443","position":12,"is_corresponding":false},{"id":5968,"name":"Matthias Kretzler","orcid":"0000-0003-4064-0582","position":13,"is_corresponding":false},{"id":281119,"name":"Ying Zheng","orcid":"0000-0003-2723-9022","position":14,"is_corresponding":false},{"id":54241,"name":"Jonathan Himmelfarb","orcid":"0000-0002-3319-1224","position":15,"is_corresponding":false},{"id":255144,"name":"Jennifer L. Harder","orcid":"0000-0002-7927-608X","position":16,"is_corresponding":false},{"id":247070,"name":"Benjamin Freedman","orcid":"0000-0003-2228-7383","position":17,"is_corresponding":false},{"id":682028,"name":"Benjamin A. Juliar","orcid":"0000-0003-4828-9053","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T01:57:36.298171Z","pmid":"38838223","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}