TWEAK/Fn14 and Non-Canonical NF-kappaB Signaling in Kidney Disease

Frontiers in Immunology
Jonay PovedaMaría D Sanchez-Niño

Abstract

The incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) is increasing. However, there is no effective therapy for AKI and current approaches only slow down, but do not prevent progression of CKD. TWEAK is a TNF superfamily cytokine. A solid base of preclinical data suggests a role of therapies targeting the TWEAK or its receptor Fn14 in AKI and CKD. In particular TWEAK/Fn14 targeting may preserve renal function and decrease cell death, inflammation, proteinuria, and fibrosis in mouse animal models. Furthermore there is clinical evidence for a role of TWEAK in human kidney injury including increased tissue and/or urinary levels of TWEAK and parenchymal renal cell expression of the receptor Fn14. In this regard, clinical trials of TWEAK targeting are ongoing in lupus nephritis. Nuclear factor-kappa B (NF-κB) activation plays a key role in TWEAK-elicited inflammatory responses. Activation of the non-canonical NF-κB pathway is a critical difference between TWEAK and TNF. TWEAK activation of the non-canonical NF-κB pathways promotes inflammatory responses in tubular cells. However, there is an incomplete understanding of the role of non-canonical NF-κB activation in kidney disease and on its contribution to TWEAK...Continue Reading

Citations

Jan 19, 2016·Biochimica Et Biophysica Acta·Jonay PovedaMaria D Sanchez-Niño
Jun 9, 2016·Expert Opinion on Investigational Drugs·Maria Vanessa Perez-GomezBeatriz Fernandez-Fernandez
Jun 30, 2016·Scientific Reports·Lara Valiño-RivasMaria D Sanchez-Niño
May 14, 2016·PloS One·M Nusrat SharifLih-Ling Lin
Jul 10, 2018·The Journal of Pathology·Cristian González-GuerreroAdrián M Ramos
Sep 27, 2019·Current Developments in Nutrition·Rattiyaporn Kanlaya, Visith Thongboonkerd
Nov 19, 2015·Cell & Bioscience·Haisong Zhang, Shao-Cong Sun
Jun 6, 2017·Nature Reviews. Immunology·Shao-Cong Sun
Jun 4, 2020·Cells·Samantha WhiteKebin Hu
Mar 4, 2020·Toxins·Sol CarriazoAlberto Ortiz
Jan 30, 2021·The Journal of Pathology·Jonay PovedaGema Ruiz-Hurtado
May 29, 2021·Clinical and Translational Medicine·Donglin SunXiaoren Zhang
Jun 23, 2021·Journal of the American Society of Nephrology : JASN·Adrian CordidoMiguel A Garcia-Gonzalez

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Methods Mentioned

BETA
ubiquitination
histone acetylation
biopsies
GTPases
nuclear translocation

Software Mentioned

TWEAK

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