TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?

Clin Sci (Lond). 2019 May 16;133(10):1145-1166. doi: 10.1042/CS20181116. Print 2019 May 31.

Abstract

Ligands and receptors of the tumor necrosis factor (TNF) superfamily regulate immune responses and homeostatic functions with potential diagnostic and therapeutic implications. Kidney disease represents a global public health problem, whose prevalence is rising worldwide, due to the aging of the population and the increasing prevalence of diabetes, hypertension, obesity, and immune disorders. In addition, chronic kidney disease is an independent risk factor for the development of cardiovascular disease, which further increases kidney-related morbidity and mortality. Recently, it has been shown that some TNF superfamily members are actively implicated in renal pathophysiology. These members include TNF-related apoptosis-inducing ligand (TRAIL), its decoy receptor osteoprotegerin (OPG), and TNF-like weaker inducer of apoptosis (TWEAK). All of them have shown the ability to activate crucial pathways involved in kidney disease development and progression (e.g. canonical and non-canonical pathways of the transcription factor nuclear factor-kappa B), as well as the ability to regulate cell proliferation, differentiation, apoptosis, necrosis, inflammation, angiogenesis, and fibrosis with double-edged effects depending on the type and stage of kidney injury. Here we will review the actions of TRAIL, OPG, and TWEAK on diabetic and non-diabetic kidney disease, in order to provide insights into their full clinical potential as biomarkers and/or therapeutic options against kidney disease.

Keywords: TRAIL and OPG; TWEAK; biomarkers; cardiovascular risk; diabetic kidney disease; non-diabetic kidney disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cytokine TWEAK / metabolism*
  • Diabetic Nephropathies / metabolism
  • Humans
  • Kidney / metabolism
  • Kidney Diseases / metabolism*
  • Osteoprotegerin / metabolism*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*

Substances

  • Biomarkers
  • Cytokine TWEAK
  • Osteoprotegerin
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF11B protein, human
  • TNFSF10 protein, human
  • TNFSF12 protein, human