Therapeutic potential of pro-resolving mediators in diabetic kidney disease

https://doi.org/10.1016/j.addr.2021.113965Get rights and content
Under a Creative Commons license
open access

Highlights

  • Inflammatory molecules play a central role in the pathogenesis of DKD.

  • Inflammation initiation and resolution is a highly regulated host response.

  • Specialized pro-resolving lipid mediators (SPMs) promote the resolution of inflammation.

  • SPMs are being investigated to treat chronic inflammation in DKD.

Abstract

Renal microvascular disease associated with diabetes [Diabetic kidney disease - DKD] is the leading cause of chronic kidney disease. In DKD, glomerular basement membrane thickening, mesangial expansion, endothelial dysfunction, podocyte cell loss and renal tubule injury contribute to progressive glomerulosclerosis and tubulointerstitial fibrosis. Chronic inflammation is recognized as a major pathogenic mechanism for DKD, with resident and circulating immune cells interacting with local kidney cell populations to provoke an inflammatory response. The onset of inflammation is driven by the release of well described proinflammatory mediators, and this is typically followed by a resolution phase. Inflammation resolution is achieved through the bioactions of endogenous specialized pro-resolving lipid mediators (SPMs). As our understanding of SPMs advances ‘resolution pharmacology’ based approaches using these molecules are being explored in DKD.

Keywords

Tubulointerstitial fibrosis
Glomerulosclerosis
Hyperglycemia
Inflammation
Specialized pro-resolving mediators
Polyunsaturated fatty acids
Lipoxins

Abbreviations

ATLs
Aspirin-triggered lipoxins
CTGF/CCN2
Connective tissue growth factor
DKD
Diabetic Kidney Disease
DHA
Docosahexaenoic acid
EPA
Eicosapentaenoic acid
eNOS
Endothelial nitric oxide synthase
ESRD
End-stage renal disease
EGF
Epidermal growth factor
ECM
Extracellular Matrix
GBM
Glomerular basement membrane
GECs
Glomerular endothelial cells
ICAM1
Intracellular adhesion molecule-1
LX
Lipoxin
LO
Lipoxygenase
MaRs
Maresins
MCP1
Monocyte chemoattractant protein-1
NP
Nanoparticles
NO
Nitric oxide
PDGF
Platelet-derived growth factor
PUFA
Polyunsaturated Fatty Acid
PMN
Polymorphonuclear leukocyte
PDs
Protectins
Rvs
Resolvin
SPM
Specialized pro-resolving mediator
TGF-β1
Transforming growth factor beta-1
TIF
Tubulointerstitial fibrosis
UAE
Urinary albumin excretion
VEGF
Vascular endothelial growth factor
VCAM1
Vascular cell adhesion molecule-1

Cited by (0)

This review is part of the Advanced Drug Delivery Reviews theme issue on "Fibrosis & Drug Delivery".