Aug 2026· Biochemical Pharmacology· Vol 253, pp.
118354
· 0 citations· 51 references
Medicine
TL;DR
Findings reveal that NETs promote glomerular endothelial injury via the cGAS-STING pathway, offering a potential therapeutic strategy for IgAN.
Abstract
IgA nephropathy (IgAN), a common primary glomerulonephritis, has an incompletely elucidated pathogenesis. Neutrophil extracellular traps (NETs), key components of innate immunity, are known to mediate renal injury in various kidney diseases, yet their role in IgAN remains unclear. In this study, we observed significantly elevated NETs levels in the serum and renal tissues of IgAN patients and mouse models, and DNase I-mediated NETs degradation attenuated glomerular injury in IgAN mice. In vitro, NETs induced injury and glycocalyx shedding in human renal glomerular endothelial cells (HRGECs), accompanied by cGAS-STING pathway activation and upregulation of downstream inflammatory factors. These effects were substantially reversed by DNase I, cGAS/STING inhibitors (RU.521/H151), or siRNA-mediated knockdown of cGAS/STING. Our findings reveal that NETs promote glomerular endothelial injury via the cGAS-STING pathway, offering a potential therapeutic strategy for IgAN.
Globally, immunoglobulin A (IgA) nephropathy (IgAN) is diagnosed more frequently than any other primary glomerular disorder and contributes substantially to the development of chronic kidney disease and end-stage renal disease. Although the Huangkui capsule, derived from Abelmoschus manihot, has demonstrated renoprotec...
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IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with a particularly high prevalence in Asia, and is a leading cause of end-stage renal disease (ESRD). The disease typically presents initially with hematuria and proteinuria, accompanied by progressive decline in renal function. The hallma...
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Endothelial dysfunction underpins the pathogenesis of sepsis-induced acute lung injury (SI-ALI), wherein neutrophil extracellular traps (NETs) serve as pivotal mediators driving excessive inflammatory responses and progressive tissue deterioration. This study aimed to elucidate the molecular mechanism by which NETs dis...
