Diabetes-associated neutrophil NETosis: pathogenesis and interventional target of diabetic complications

Abstract

Neutrophil extracellular traps (NETs) are known as extracellular fibers networks consisting of antimicrobial proteins and decondensated chromatin DNA released by activated neutrophils. NETosis is a NETs-induced neutrophilic cell death which is unique from necrosis or apoptosis. Besides its neutralizing pathogen, NETosis plays a crucial role in diabetes and diabetes-related complications. In patients with diabetes, NETs-releasing products are significantly elevated in blood, and these findings confirm the association of NETosis and diabetic complications, including diabetic wound healing, diabetic retinopathy, and atherosclerosis. This article briefly summarizes the mechanisms of NETosis and discusses its contribution to the pathogenesis of diabetes-related complications and suggests new therapeutic targets by some small molecule compounds.

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy

“…Diabetic foot complications often manifest in the advanced stages of DPN. Presently, the precise pathogenesis of DMC remains elusive in modern medicine and is likely associated with inflammatory responses, oxidative stress, vascular endothelial cell damage, and alterations in vascular permeability due to elevated glucose levels ( Singh and Kulkarni, 2022 ; Zhu et al, 2023 ). Current clinical treatments for DMC primarily target these factors but exhibit limited efficacy ( Nellaiappan et al, 2022 ).…”

Changes in Circulating Acylated Ghrelin and Neutrophil Elastase in Diabetic Retinopathy

“…These circulating cells play a very important defensive role in the first steps of hyperglycemia-induced acute inflammation, via the degranulation, phagocytosis, and extrusion of neutrophil extracellular traps (NETs) [25]. However, during chronic inflammation, the exacerbated presence of neutrophils and NETs is associated with the thickening of the retinal vascular basement membrane, loss of pericytes, and alterations in the blood-retinal barrier, which, combined, trigger DR microvascular and macrovascular complications [25][26][27][28][29][30][31]. Interestingly, by binding to GHSR-1a on neutrophils, ghrelin is able to promote their apoptosis [22,23], potentially impacting DR microvascular complications in diabetic patients.…”