Neutrophil extracellular traps promote NLRP3 inflammasome activation and glomerular endothelial dysfunction in diabetic kidney disease
Diabetes mellitus is a metabolic disease largely due to lifestyle and nutritional imbalance, resulting in insulin resistance, hyperglycemia and vascular complications. Diabetic kidney disease (DKD) is a major cause of end-stage renal failure contributing to morbidity and mortality worldwide. Therape...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
20 July 2022
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| In: |
Nutrients
Year: 2022, Jahrgang: 14, Heft: 14, Pages: 1-15 |
| ISSN: | 2072-6643 |
| DOI: | 10.3390/nu14142965 |
| Online-Zugang: | Resolving-System, kostenfrei: https://doi.org/10.3390/nu14142965 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6643/14/14/2965 
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| Verfasserangaben: | Anubhuti Gupta, Kunal Singh, Sameen Fatima, Saira Ambreen, Silke Zimmermann, Ruaa Younis, Shruthi Krishnan, Rajiv Rana, Ihsan Gadi, Constantin Schwab, Ronald Biemann, Khurrum Shahzad, Vibha Rani, Shakir Ali, Peter Rene Mertens, Shrey Kohli and Berend Isermann |
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| 245 | 1 | 0 | |a Neutrophil extracellular traps promote NLRP3 inflammasome activation and glomerular endothelial dysfunction in diabetic kidney disease |c Anubhuti Gupta, Kunal Singh, Sameen Fatima, Saira Ambreen, Silke Zimmermann, Ruaa Younis, Shruthi Krishnan, Rajiv Rana, Ihsan Gadi, Constantin Schwab, Ronald Biemann, Khurrum Shahzad, Vibha Rani, Shakir Ali, Peter Rene Mertens, Shrey Kohli and Berend Isermann |
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| 520 | |a Diabetes mellitus is a metabolic disease largely due to lifestyle and nutritional imbalance, resulting in insulin resistance, hyperglycemia and vascular complications. Diabetic kidney disease (DKD) is a major cause of end-stage renal failure contributing to morbidity and mortality worldwide. Therapeutic options to prevent or reverse DKD progression are limited. Endothelial and glomerular filtration barrier (GFB) dysfunction and sterile inflammation are associated with DKD. Neutrophil extracellular traps (NETs), originally identified as an innate immune mechanism to combat infection, have been implicated in sterile inflammatory responses in non-communicable diseases. However, the contribution of NETs in DKD remains unknown. Here, we show that biomarkers of NETs are increased in diabetic mice and diabetic patients and that these changes correlate with DKD severity. Mechanistically, NETs promote NLRP3 inflammasome activation and glomerular endothelial dysfunction under high glucose stress in vitro and in vivo. Inhibition of NETs (PAD4 inhibitor) ameliorate endothelial dysfunction and renal injury in DKD. Taken together, NET-induced sterile inflammation promotes diabetes-associated endothelial dysfunction, identifying a new pathomechanism contributing to DKD. Inhibition of NETs may be a promising therapeutic strategy in DKD. | ||
| 650 | 4 | |a diabetic kidney disease | |
| 650 | 4 | |a endothelial dysfunction | |
| 650 | 4 | |a glomerular endothelial cells | |
| 650 | 4 | |a glomerular filtration barrier disruption | |
| 650 | 4 | |a neutrophil extracellular traps | |
| 650 | 4 | |a NLRP3 inflammasome | |
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