Relevance of the Pyroptosis-Related Inflammasome Pathway in the Pathogenesis of Diabetic Kidney Disease

Abstract

Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD) in many developed and developing countries. Pyroptosis is a recently discovered form of programmed cell death (PCD). With progress in research on DKD, researchers have become increasingly interested in elucidating the role of pyroptosis in DKD pathogenesis. This review focuses on the three pathways of pyroptosis generation: the canonical inflammasome, non-canonical inflammasome, and caspase-3-mediated inflammasome pathways. The molecular and pathophysiological mechanisms of the pyroptosis-related inflammasome pathway in the development of DKD are summarized. Activation of the diabetes-mediated pyroptosis-related inflammasomes, such as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Toll-like receptor 4 (TLR4), caspase-1, interleukin (IL)-1β, and the IL-18 axis, plays an essential role in DKD lesions. By inhibiting activation of the TLR4 and NLRP3 inflammasomes, the production of caspase-1, IL-1β, and IL-18 is inhibited, thereby improving the pathological changes associated with DKD. Studies using high-glucose–induced cell models, high-fat diet/streptozotocin-induced DKD animal models, and human biopsies will help determine the spatial and temporal expression of DKD inflammatory components. Recent studies have confirmed the relationship between the pyroptosis-related inflammasome pathway and kidney disease. However, these studies are relatively superficial at present, and the mechanism needs further elucidation. Linking these findings with disease activity and prognosis would provide new ideas for DKD research.

Total Flavones of Abelmoschus manihot Ameliorates Podocyte Pyroptosis and Injury in High Glucose Conditions by Targeting METTL3-Dependent m6A Modification-Mediated NLRP3-Inflammasome Activation and PTEN/PI3K/Akt Signaling

“…However, it is reported that gasdermin E (GSDME) cleavage by caspase-3 liberates the GSDME-N domain and mediates pyroptosis by forming pores in the plasma membrane. Caspase-3-mediated inflammasome pathway is also a pathway of pyroptosis generation in DKD (Liu et al, 2021). The effect of TFA in regulating apoptosis and caspase-3-mediated inflammasome pathway will be focused in our further study.…”

Ferroptosis: A New Regulatory Mechanism in Osteoporosis

“…It is initiated by oxidative perturbations in the intracellular microenvironment, which are constitutively controlled by glutathione peroxidase 4 (GPX4) and can be inhibited by iron-chelating agents and lipophilic antioxidants [ 9 ]. Ferroptosis is distinguished from apoptosis [ 10 ], necrosis [ 11 ], autophagy [ 12 ], and pyroptosis [ 13 ] by a varying set of morphological characteristics, inducing factors, and regulatory pathways.…”

The advanced glycation end-products (AGEs)/ROS/NLRP3 inflammasome axis contributes to delayed diabetic corneal wound healing and nerve regeneration

“…In addition to inflammatory cascades, the activated NLRP3 inflammasome also promoted GSDMD-executed pyroptosis, a kind of programmed cell death [7,14,15]. Several lines of studies indicated that pyroptosis was involved in the pathogenesis of diabetes and its complications, such as diabetic nephropathy [49,50], diabetic retinopathy [51][52][53], and diabetic cardiomyopathy [18,54,55]. However, whether GSDMD-executed pyroptosis was involved in the pathogenesis of DK remained unknown.…”