RT Journal Article
T1 TNF-related weak inducer of apoptosis (TWEAK) regulates junctional proteins in tubular epithelial cells via canonical NF-κB pathway and ERK activation
A1 Berzal, Sergio
A1 González Guerrero, Cristian
A1 Rayego Mateos, Sandra
A1 Ucero Herrería, Álvaro Conrado
A1 Ocaña Salceda, Carlos
A1 Egido, Jesús
A1 Ortiz, Alberto
A1 Ruíz Ortega, Marta
A1 Ramos, Adrián M.
AB The tubular epithelium may be intrinsically involved in promoting kidney injury by junctional instability, epithelial-mesenchymal transition (EMT) and extracellular matrix remodelling. In this work, we investigated whether the pleiotropic and proinflammatory cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK), could be able to disturb junctional protein expression and to induce EMT of tubular cells. In cultured murine proximal tubular cells TWEAK induced phenotypic changes that were accompanied by F-actin redistribution, loss of epithelial adherent (E-cadherin, Cadherin-16, β-catenin) and tight junction (ZO-1) proteins, and re-expression of the mesenchymal protein Vimentin. The transcriptional repressors Snail and HNF1β were also modulated by TWEAK. In a murine model of obstructive renal pathology, TWEAK expression correlated with the appearance of the mesenchymal marker αSMA in kidney tubular cells. Mechanistically, the epithelial changes induced by TWEAK, including loss of epithelial integrity and EMT, via Fn14 were TGF-β1 independent, but mediated by several intracellular signaling systems, including the canonical NF-κB, ERK activation and the vitamin D receptor modulation. These results highlight potential contributions of TWEAK-induced inflammatory mechanisms that could unveil new pathogenic effects of TWEAK starting tubulointerstitial damage and fibrosis.
PB Wiley
SN 0021-9541
YR 2014
FD 2014-12-23
LK https://hdl.handle.net/20.500.14352/133179
UL https://hdl.handle.net/20.500.14352/133179
LA eng
NO Ortiz A, Sanz AB, Sanchez-Niño MD, Izquierdo MC, Ucero AC, Egido J, Ruiz-Ortega M, Ramos AM, Putterman C. TNF-related weak inducer of apoptosis (TWEAK) regulates junctional proteins in tubular epithelial cells via canonical NF-κB pathway and ERK activation. Journal of Physiology. 2015;593(18):4149-4165. doi:10.1113/JP270164. PMID: 26105038.
NO Instituto de Salud Carlos III
NO Unión Europea
NO Comunidad Autónoma de Madrid
NO Instituto Reina Sofia de Investigación Nefrológica
DS Docta Complutense
RD 20 mar 2026