TNF receptors: signaling pathways and contribution to renal dysfunction

Kidney Int. 2015 Feb;87(2):281-96. doi: 10.1038/ki.2014.285. Epub 2014 Aug 20.


Tumor necrosis factor (TNF), initially reported to induce tumor cell apoptosis and cachexia, is now considered a central mediator of a broad range of biological activities from cell proliferation, cell death and differentiation to induction of inflammation and immune modulation. TNF exerts its biological responses via interaction with two cell surface receptors: TNFR1 and TNFR2. (TNFRs). These receptors trigger shared and distinct signaling pathways upon TNF binding, which in turn result in cellular outputs that may promote tissue injury on one hand but may also induce protective, beneficial responses. Yet the role of TNF and its receptors specifically in renal disease is still not well understood. This review describes the expression of the TNFRs, the signaling pathways induced by them and the biological responses of TNF and its receptors in various animal models of renal diseases, and discusses the current outcomes from use of TNF biologics and TNF biomarkers in renal disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism
  • Animals
  • Carcinoma, Renal Cell / etiology
  • Carcinoma, Renal Cell / metabolism
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Graft Rejection / etiology
  • Graft Rejection / metabolism
  • Humans
  • Kidney Diseases / etiology*
  • Kidney Diseases / metabolism*
  • Kidney Diseases / therapy
  • Kidney Neoplasms / etiology
  • Kidney Neoplasms / metabolism
  • Kidney Transplantation / adverse effects
  • Models, Biological
  • Nephritis / etiology
  • Nephritis / metabolism
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism
  • Ureteral Obstruction / complications
  • Ureteral Obstruction / metabolism


  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha