TNF receptors: signaling pathways and contribution to renal dysfunction

Rafia S Al-Lamki; Tanya N Mayadas

doi:10.1038/ki.2014.285

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.

Authors

Rafia S Al-Lamki¹, Tanya N Mayadas²

Affiliations

¹ Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
² Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital, Boston, MA USA.

PMID: 25140911
DOI: 10.1038/ki.2014.285

Abstract

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

Substances

Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha