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已发表论文
糖尿病肾病中的中性粒细胞胞外诱捕网：发病机制和新兴治疗策略
Authors Wang B, Zhang R , Liu X, Shang Y, Jin T , Gao C, Yang N, Jin J, He Q
Received 20 November 2025
Accepted for publication 12 February 2026
Published 21 February 2026 Volume 2026:20 583077
DOI https://doi.org/10.2147/DDDT.S583077
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Tuo Deng
Binqi Wang,1,2,* Ruikai Zhang,1,2,* Xinbo Liu,1,2 Yiwei Shang,1,2 Taian Jin,1,2 Chan Gao,1,2 Nan Yang,1,2 Juan Jin,1,2 Qiang He1,2
1Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China; 2Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease, Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology, Hangzhou, Zhejiang, 310006, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qiang He, Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China, Email qianghe1973@126.com Juan Jin, Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China, Email lang_018@163.com
Abstract: Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus and the leading global cause of end-stage renal disease. While chronic hyperglycemia and classic metabolic pathways such as protein kinase C activation, advanced glycation end product (AGE) accumulation, and renin–angiotensin system overactivity elucidate many features of DKD, they do not fully account for its complex inflammatory pathology. Recent studies have highlighted neutrophil extracellular trap (NET) formation, or NETosis, as a critical mechanism linking metabolic stress to immune dysregulation in DKD. NETosis is a specialized form of programmed cell death in neutrophils that releases web-like chromatin structures decorated with histones, elastase, and myeloperoxidase. Although these structures function as protective barriers against pathogens, they become pathogenic when dysregulated. In the diabetic milieu, hyperglycemia, advanced glycation end products (AGEs), protein kinase C signaling, lipid abnormalities, and pro-inflammatory cytokines all promote excessive NETosis. Once formed, NETs drive renal injury by inducing endothelial dysfunction, podocyte and tubular epithelial cell damage, macrophage activation, and profibrotic signaling, thereby accelerating inflammation, fibrosis, and renal decline. Therapeutic strategies targeting NETosis are emerging, including inhibitors of PAD4, NADPH oxidase, and neutrophil elastase, as well as NET-degrading agents such as DNase I and histone-neutralizing compounds. Classical antidiabetic drugs, notably metformin and GLP-1 receptor agonists, also show potential in modulating NET formation. Collectively, these insights position NETosis as both a biomarker and a therapeutic target in DKD, offering novel opportunities to mitigate diabetes-associated renal complications.
Keywords: diabetic kidney disease, kidney injury, neutrophil extracellular traps, NETosis, inflammation, therapeutic targets
1Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China; 2Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease, Zhejiang-Macau International Joint Laboratory of Integrated Traditional Chinese and Western Medicine for Nephrology and Immunology, Hangzhou, Zhejiang, 310006, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qiang He, Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China, Email qianghe1973@126.com Juan Jin, Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China, Email lang_018@163.com
Abstract: Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus and the leading global cause of end-stage renal disease. While chronic hyperglycemia and classic metabolic pathways such as protein kinase C activation, advanced glycation end product (AGE) accumulation, and renin–angiotensin system overactivity elucidate many features of DKD, they do not fully account for its complex inflammatory pathology. Recent studies have highlighted neutrophil extracellular trap (NET) formation, or NETosis, as a critical mechanism linking metabolic stress to immune dysregulation in DKD. NETosis is a specialized form of programmed cell death in neutrophils that releases web-like chromatin structures decorated with histones, elastase, and myeloperoxidase. Although these structures function as protective barriers against pathogens, they become pathogenic when dysregulated. In the diabetic milieu, hyperglycemia, advanced glycation end products (AGEs), protein kinase C signaling, lipid abnormalities, and pro-inflammatory cytokines all promote excessive NETosis. Once formed, NETs drive renal injury by inducing endothelial dysfunction, podocyte and tubular epithelial cell damage, macrophage activation, and profibrotic signaling, thereby accelerating inflammation, fibrosis, and renal decline. Therapeutic strategies targeting NETosis are emerging, including inhibitors of PAD4, NADPH oxidase, and neutrophil elastase, as well as NET-degrading agents such as DNase I and histone-neutralizing compounds. Classical antidiabetic drugs, notably metformin and GLP-1 receptor agonists, also show potential in modulating NET formation. Collectively, these insights position NETosis as both a biomarker and a therapeutic target in DKD, offering novel opportunities to mitigate diabetes-associated renal complications.
Keywords: diabetic kidney disease, kidney injury, neutrophil extracellular traps, NETosis, inflammation, therapeutic targets