ArticleCell reports2024
Interferon-γ induces combined pyroptotic angiopathy and APOL1 expression in human kidney disease.
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Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Differential regulation of basal and interferon-inducedAmerican journal of physiology. Renal physiology · 2026Article
- DIA proteomics of FFPE renal biopsies reveals two molecular subtypes of lupus nephritis and identifies APOL1 as candidate biomarker for stratification.Lupus science & medicine · 2026Article
- Genetic kidney disease in adults-the pathologists' perspective.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Review
- Immune hyperactivity in hemodialysis patients is associated with interferon gamma-induced trained immunity.iScience · 2026Article
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Endothelial prolyl hydroxylase 3 mitigates maladaptive inflammation to promote post-ischemic kidney repair.Kidney international · 2026Article
- Microenvironment optimization enables kidney organoid longevity with epithelial-endothelial joint basement membrane formation.bioRxiv : the preprint server for biology · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- APOL1 Genotype and Patient Outcomes in US and South African Transplant Recipients With HIV who Received Kidneys From Donors With HIV.Transplantation · 2026Article
- Calcium Shock Enables Efficient and Programmable Particle Delivery for Genome Editing Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Organoids Gone Viral: A Comprehensive Review on Human Organoid Models to Study Viral Pathogenesis.Viruses · 2026Review
- A novel diagnostic model for HIV-HTN comorbidity: genomic discovery, clinical validation, and mechanistic elucidation.Frontiers in medicine · 2026Article
- APOL1-mediated kidney disease: a narrative review of the lessons learnt from the past 15 years.BMC nephrology · 2025Review
- Modelling APOL1-mediated kidney inflammation and fibrosis using a partially reprogrammed urine-derived SIX2-positive renal progenitor cell line.Stem cell research & therapy · 2025Article
- APOL1 risk variants induce metabolic reprogramming of podocytes in patient-derived kidney organoids.Stem cell reports · 2025Article
- Article
- CRISPR and gene editing for kidney diseases: where are we?Clinical kidney journal · 2025Review
- Article
- Review
- Single cell sequencing and spatial multiomics of diabetic kidney segmentation insights zonation-specific therapeutic metabolic pathways.Cell insight · 2025Article
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Authors and funding
18 authors.
Benjamin A JuliarDivision of Nephrology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
Ian B StanawayDivision of Nephrology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA.
Fumika SanoDivision of Nephrology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
Hongxia FuInstitute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Division of Hematology, Department of Medicine, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington School of Medicine, Seattle, WA 98109, USA; Bloodworks Northwest Research Institute, Seattle, WA 98102, USA; Plurexa, Seattle, WA 98109, USA.
Kelly D SmithDivision of Nephrology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Shreeram AkileshKidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98109, USA.
Suzie J ScalesDepartment of Immunology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
Jamal El SaghirDivision of Nephrology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Pavan K BhatrajuKidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
Esther LiuDivision of Nephrology and Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Johnson YangDivision of Nephrology and Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Jennie LinDivision of Nephrology and Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Sean EddyDivision of Nephrology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Matthias KretzlerDivision of Nephrology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Ying ZhengKidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington School of Medicine, Seattle, WA 98109, USA.
Jonathan HimmelfarbDivision of Nephrology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA.
Jennifer L HarderDivision of Nephrology, Department of Internal Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: jharder@med.umich.edu.
Benjamin S FreedmanDivision of Nephrology, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Kidney Research Institute, University of Washington School of Medicine, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Bioengineering, University of Washington School of Medicine, Seattle, WA 98109, USA; Plurexa, Seattle, WA 98109, USA. Electronic address: benof@uw.edu.
Funding
Using iPSCs to model patient outcomes in nephrotic syndromeUH3TR000504 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2014 to 2016
$6.1MTranslational center for kidney microphysiological systems to improve drug safety and efficacyU2CTR004867 · NCATS · UNIVERSITY OF WASHINGTON · PI Benjamin Solomon Freedman, Jonathan Himmelfarb · 2024 to 2026
$4.8MTissue Chip Data to the Microphysiology Systems Database (MPS-Db) Supplement to A Microphysiological System for Kidney Disease Modeling and Drug Efficacy TestingUH3TR002158 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2019 to 2021
$4.2MTraining Core for Chicago KUH FORWARDTL1DK132769 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Tamara Isakova · 2021 to 2026
$4.0MCell specific delivery of novel therapies to enhance glomerular regeneration and repairUC2DK126006 · NIDDK · UNIVERSITY OF WASHINGTON · PI SHANKLAND, STUART JAMES · 2020 to 2024
$4.0MMechanisms of interactions between von Willebrand factor and its binding partnersR01HL167688 · NHLBI · UNIVERSITY OF WASHINGTON · PI Hongxia Fu · 2023 to 2026
$2.7MSafety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological SystemsUH3TR003288 · NCATS · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON, HIMMELFARB, JONATHAN · 2022 to 2024
$2.3MSCGE Comparative Studies SupplementU01DK127553 · NIDDK · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2020 to 2022
$2.2MUnveiling Functional Roles of Apical Surface Interactions Between Opposing Cell LayersR35GM149516 · NIGMS · UNIVERSITY OF WASHINGTON · PI Hongxia Fu · 2023 to 2026
$1.8MA Human Organoid Model of Polycystic Kidney DiseaseR01DK117914 · NIDDK · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2018 to 2022
$1.8MMechanisms of Kidney Injury in COVID-19R01DK130386 · NIDDK · UNIVERSITY OF WASHINGTON · PI AKILESH, SHREERAM, FREEDMAN, BENJAMIN SOLOMON · 2021 to 2023
$1.2MUtility of Human Organoids for Safety and Efficiency Evaluations of Genome Editing TherapeuticsU01AI176460 · NIAID · UNIVERSITY OF WASHINGTON · PI FREEDMAN, BENJAMIN SOLOMON · 2023 to 2025
$1.0MNCATS NIH HHS U2C TR004867NCATS NIH HHS UH3 TR000504NCATS NIH HHS UH3 TR002158NCATS NIH HHS UH3 TR003288NHLBI NIH HHS R01 HL167688NIAID NIH HHS U01 AI176460NIDDK NIH HHS R01 DK117914NIDDK NIH HHS R01 DK130386NIDDK NIH HHS TL1 DK132769NIDDK NIH HHS U01 DK127553NIDDK NIH HHS UC2 DK126006NIGMS NIH HHS R35 GM149516
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.
Indexed as
Apolipoprotein L1Interferon-gammaKidney DiseasesPyroptosisCOVID-19Endothelial CellsHumansKidneySARS-CoV-2Signal TransductionAPOL1 protein, humanApolipoprotein L1IFNG protein, humanInterferon-gammabaricitinibcaspasecell deathCP: Cell biologyCP: Immunologygasderminglomerulosclerosisinflammationpodocalyxinproteomicspyroptosisspatial transcriptomics
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