The Role of the NLRP3 Inflammasome in Mediating Glomerular and Tubular Injury in Diabetic Nephropathy

Williams, Bethany M, Cliff, Chelsy L, Lee, Kelvin , Squires, Paul and Hills, Claire (2022) The Role of the NLRP3 Inflammasome in Mediating Glomerular and Tubular Injury in Diabetic Nephropathy. Frontiers in Physiology (Metabolic Physiology), 13 (907504). ISSN 1664-042X

Full content URL: https://doi.org/10.3389/fphys.2022.907504

Documents
The Role of the NLRP3 Inflammasome in Mediating Glomerular and Tubular Injury in Diabetic Nephropathy
Published Open Access manuscript
[img]
[Download]
[img]
Preview
PDF
fphys-13-907504.pdf - Whole Document
Available under License Creative Commons Attribution 4.0 International.

1MB
Item Type:Article
Item Status:Live Archive

Abstract

The NOD-like receptor protein 3 (NLRP3) inflammasome is a multi-protein signalling complex integral to the chronic inflammatory response, activated in response to sterile and non-sterile cellular damage. The assembly and activation of the NLRP3 inflammasome comprise a two-step process involving nuclear factor kappa B (NFkB)-mediated priming, followed by canonical, non-canonical or alternative signalling pathways. These result in the maturation and release of inflammatory cytokines interleukin 1 beta (IL1ß) and interleukin- 18 (IL18), which are associated with chronic inflammatory conditions including diabetic kidney disease. Diabetic nephropathy is a condition affecting ~40% of people with diabetes, the key underlying pathology of which is tubulointerstitial inflammation and fibrosis. There is growing evidence to suggest the involvement of the NLRP3 inflammasome in this chronic inflammation. Early deterioration of kidney function begins in the glomerulus, with tubular inflammation dictating the progression of late- stage disease. Priming and activation of the NLRP3 inflammasome have been linked to several clinical markers of nephropathy including proteinuria and albuminuria, in addition to morphological changes including mesangial expansion. Treatment options for diabetic nephropathy are limited, and research that examines the impact of directly targeting the NLRP3 inflammasome, or associated downstream components are beginning to gain favour, with several agents currently in clinical trials. This review will explore a role for NLRP3 inflammasome activation and signalling in mediating inflammation in diabetic nephropathy, specifically in the glomerulus and proximal tubule, before briefly describing the current position of therapeutic research in this field.

Keywords:Inflammation, Diabetic nephropathy, NLRP3, diabetes, fibrosis
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
C Biological Sciences > C130 Cell Biology
B Subjects allied to Medicine > B120 Physiology
Divisions:College of Science > School of Life Sciences
Related URLs:
ID Code:49742
Deposited On:21 Jun 2022 10:24

Repository Staff Only: item control page