ArticleThe Journal of clinical investigation2021
The key role of NLRP3 and STING in APOL1-associated podocytopathy.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 131 citations in OpenAlex.
- Nucleic acid sensing pathways in kidney disease development.Nature reviews. Nephrology · 2026Review
- Update on APOL1 and chronic kidney diseases in children.Pediatric nephrology (Berlin, Germany) · 2026Review
- Review
- APOL1 kidney disease: a critical narrative review of molecular mechanisms, clinical heterogeneity, and the emerging therapeutic landscape.International urology and nephrology · 2026Review
- APOL1 risk alleles modulate T cell receptor signaling to promote allograft rejection.The Journal of clinical investigation · 2026Article
- Apolipoproteins L involvement in immunity.Journal of human immunity · 2026Review
- Proteomic risk score for early prediction of kidney disease progression in individuals with APOL1 high-risk genotypes.Nature medicine · 2026Article
- Nephrotic syndrome genomic discovery in the Mass General Brigham Biobank identifies monoallelic MEFV variants as a risk factor for focal segmental glomerulosclerosis.Kidney international · 2026Article
- The spatiotemporal dynamics of MAMs: mechanisms, pathologies, and therapeutic rewiring.Cellular & molecular biology letters · 2026Review
- Emerging Mechanistic Roles of STING Signaling in Kidney Diseases.The American journal of pathology · 2026Review
- Hyperlipidemia in membranous nephropathy.Clinical kidney journal · 2026Review
- Podocyte Metabolic Reprogramming and Targeted Therapy.Journal of the American Society of Nephrology : JASN · 2026Review
- Macrophage retrotransposon expression is associated with lupus.Genes and immunity · 2026Article
- cGAS-STING pathway in innate immunity and its cell-specific role in kidney diseases.Frontiers in immunology · 2026Review
- Podocyte-specific acid sphingomyelinase overexpression promotes gasdermin D dependent pyroptosis by impairing autophagic flux during obesity.Frontiers in physiology · 2026Article
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- APOL1-mediated kidney disease: a narrative review of the lessons learnt from the past 15 years.BMC nephrology · 2025Review
- Podocytopathies.Nature reviews. Disease primers · 2025Review
- Tanshinone IIA reduces tubulointerstitial fibrosis by suppressing GSDMD-mediated pyroptosis.Pharmaceutical biology · 2025Article
- Long non-coding RNA NEAT1 mediated lupus nephritis induced podocytes pyroptosis through DNMT1-STING axis.Renal failure · 2025Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Coding variants in apolipoprotein L1 (APOL1), termed G1 and G2, can explain most excess kidney disease risk in African Americans; however, the molecular pathways of APOL1-induced kidney dysfunction remain poorly understood. Here, we report that expression of G2 APOL1 in the podocytes of Nphs1rtTA/TRE-G2APOL1 (G2APOL1) mice leads to early activation of the cytosolic nucleotide sensor, stimulator of interferon genes (STING), and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. STING and NLRP3 expression was increased in podocytes from patients with high-risk APOL1 genotypes, and expression of APOL1 correlated with caspase-1 and gasdermin D (GSDMD) levels. To demonstrate the role of NLRP3 and STING in APOL1-associated kidney disease, we generated transgenic mice with the G2 APOL1 risk variant and genetic deletion of Nlrp3 (G2APOL1/Nlrp3 KO), Gsdmd (G2APOL1/Gsdmd KO), and STING (G2APOL1/STING KO). Knockout mice displayed marked reduction in albuminuria, azotemia, and kidney fibrosis compared with G2APOL1 mice. To evaluate the therapeutic potential of targeting NLRP3, GSDMD, and STING, we treated mice with MCC950, disulfiram, and C176, potent and selective inhibitors of NLRP3, GSDMD, and STING, respectively. G2APOL1 mice treated with MCC950, disulfiram, and C176 showed lower albuminuria and improved kidney function even when inhibitor treatment was initiated after the development of albuminuria.
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