Roles of tumour necrosis factor-related weak inducer of apoptosis/fibroblast growth factor-inducible 14 pathway in lupus nephritis

Nephrology (Carlton). 2017 Feb;22(2):101-106. doi: 10.1111/nep.12957.

Abstract

As one of the manifestations of patients with systemic lupus erythematosus, lupus nephritis (LN) has high morbidity and mortality. Although the explicit mechanism of LN remains to be fully elucidated, there is increasing evidence to support the notion that tumour necrosis factor-related weak inducer of apoptosis (TWEAK), acting via its sole receptor, fibroblast growth factor-inducible 14 (Fn14), plays a pivotal role in such pathologic process. TWEAK/Fn14 interactions occur prominently in kidneys of LN, inducing inflammatory responses, angiogenesis, mesangial proliferation, filtration barrier injuries, renal fibrosis, etc. This review will specify the important roles of TWEAK/Fn14 pathway in the pathogenesis of LN with experimental data from cellular and animal models. Additionally, the raised levels of urinary and serum soluble TWEAK correlate with renal disease activity in patients with LN. The neutralizing antibodies targeting TWEAK or other approaches inhibiting TWEAK/Fn14 signals can attenuate renal damage in the murine lupus models. Therefore, to focus on TWEAK/Fn14 signalling may be promising in both clinical evaluation and the treatment of patients with LN.

Keywords: fibroblast growth factor-inducible 14; glomerular basement membrane; lupus nephritis; proinflammatory cytokines; tumour necrosis factor-related weak inducer of apoptosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Proliferation
  • Cytokine TWEAK
  • Disease Models, Animal
  • Fibrosis
  • Humans
  • Inflammation Mediators / metabolism
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney / physiopathology
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / metabolism*
  • Lupus Nephritis / pathology
  • Lupus Nephritis / physiopathology
  • Molecular Targeted Therapy
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction* / drug effects
  • TWEAK Receptor
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factors / metabolism*

Substances

  • Cytokine TWEAK
  • Inflammation Mediators
  • Receptors, Tumor Necrosis Factor
  • TNFRSF12A protein, human
  • TNFSF12 protein, human
  • TWEAK Receptor
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factors