ArticleClinical science (London, England : 1979)2022
Adverse renal effects of NLRP3 inflammasome inhibition by MCC950 in an interventional model of diabetic kidney disease.
Article in Clinical science (London, England : 1979), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- High-salt diet in macrophage-associated metabolic disorders: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- Targeting pyroptosis in renal fibrosis: From molecular mechanisms to therapeutic horizons (Review).International journal of molecular medicine · 2026Review
- Podocyte Metabolic Reprogramming and Targeted Therapy.Journal of the American Society of Nephrology : JASN · 2026Review
- Stimulator of Interferon Genes Is a Fine-Tuner, but Not a Prime Mover, of Kidney Inflammation.The American journal of pathology · 2026Article
- [Immunometabolic disorders in type 2 diabetes mellitus mediated by NLRP3 inflammasome activation and methods of pharmacological correction thereof].Problemy endokrinologii · 2026Review
- Targeting the NLRP3 inflammasome alleviates the comorbidity of chronic pain and depression via enhancing the autophagy.Scientific reports · 2026Article
- Advances in infection-immunity mechanisms and molecular regulatory networks in severe pneumonia-associated lung injury.Frontiers in immunology · 2026Review
- PANoptosis: A novel therapeutic target in kidney disease (Review).International journal of molecular medicine · 2025Review
- Mechanisms of NLRP3 inflammasome in chronic kidney disease and the effects of traditional Chinese medicines.Renal failure · 2025Review
- Mechanistic Characterization of a Small Molecule as a Direct NLRP3 Inhibitor via Binding to the NACHT Domain.Journal of medicinal chemistry · 2025Article
- Cardiorenal Syndrome: Molecular Pathways Linking Cardiovascular Dysfunction and Chronic Kidney Disease Progression.International journal of molecular sciences · 2025Review
- Reactive Oxygen Species as a Common Pathological Link Between Alcohol Use Disorder and Alzheimer's Disease with Therapeutic Implications.International journal of molecular sciences · 2025Review
- Transformation of acute kidney injury to chronic kidney disease: the interaction between mitophagy and NLRP3 inflammasome.Frontiers in molecular biosciences · 2025Review
- Therapy Targeted to the NLRP3 Inflammasome in Chronic Kidney Disease.Kidney diseases (Basel, Switzerland) · 2024Review
- Role of the Innate Immune Response in Glomerular Disease Pathogenesis: Focus on Podocytes.Cells · 2024Review
- Renal macrophages and NLRP3 inflammasomes in kidney diseases and therapeutics.Cell death discovery · 2024Review
- New Insights on NLRP3 Inflammasome: Mechanisms of Activation, Inhibition, and Epigenetic Regulation.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Review
- The NLRP3 Inflammasome as a Pathogenic Player Showing Therapeutic Potential in Rheumatoid Arthritis and Its Comorbidities: A Narrative Review.International journal of molecular sciences · 2024Review
- Adenine model of chronic renal failure in rats to determine whether MCC950, an NLRP3 inflammasome inhibitor, is a renopreventive.BMC nephrology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome has been reported in diabetic complications including diabetic kidney disease (DKD). However, it remains unknown if NLRP3 inhibition is renoprotective in a clinically relevant interventional approach with established DKD. We therefore examined the effect of the NLRP3-specific inhibitor MCC950 in streptozotocin-induced diabetic mice to measure the impact of NLRP3 inhibition on renal inflammation and associated pathology in DKD. We identified an adverse effect of MCC950 on renal pathology in diabetic animals. Indeed, MCC950-treated diabetic animals showed increased renal inflammation and macrophage infiltration in association with enhanced oxidative stress as well as increased mesangial expansion and glomerulosclerosis when compared with vehicle-treated diabetic animals. Inhibition of the inflammasome by MCC950 in diabetic mice led to renal up-regulation of markers of inflammation (Il1β, Il18 and Mcp1), fibrosis (Col1, Col4, Fn1, α-SMA, Ctgf and Tgfβ1) and oxidative stress (Nox2, Nox4 and nitrotyrosine). In addition, enhanced glomerular accumulation of pro-inflammatory CD68 positive cells and pro-oxidant factor nitrotyrosine was identified in the MCC950-treated diabetic compared with vehicle-treated diabetic animals. Collectively, in this interventional model of established DKD, NLRP3 inhibition with MCC950 did not show renoprotective effects in diabetic mice. On the contrary, diabetic mice treated with MCC950 exhibited adverse renal effects particularly enhanced renal inflammation and injury including mesangial expansion and glomerulosclerosis.
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