TWEAKing renal injury.
TWEAK is a recently identified cytokine of the TNF superfamiliy. Through activation of the Fn14 receptor, TWEAK regulates cell proliferation, cell death and inflammation. Recent studies show increased TWEAK and Fn14 expression in tubular cells during acute kidney injury as well as elevated urinary TWEAK levels in patients with active lupus nephritis. Furthermore, glomerular mesangial cells and renal tubular epithelial cells express the Fn14 receptor under the regulation of proinflammatory cytokines. TWEAK weakly increases cell death and promotes secretion of inflammatory mediators in non-stimulated mesangial cells. In addition, in a proinflammatory milieu, TWEAK induces apoptosis of mesangial and tubular cells. The available data suggest that TWEAK is a new player in kidney injury both at the glomerular and tubulointerstitial levels and might be a target for therapeutic intervention.
Sanz
Ana Belen
AB
Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, 2040 Madrid, Spain.
Moreno
Juan Antonio
JA
Sanchez-Nino
Maria Dolores
MD
Ucero
Alvaro C
AC
Benito
Alberto
A
Santamaria
Beatriz
B
Justo
Pilar
P
Izquierdo
M Concepcion
MC
Egido
Jesus
J
Blanco-Colio
Luis Miguel
LM
Ortiz
Alberto
A
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D049109:Cell Proliferation; D000074049:Cytokine TWEAK; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000378:metabolism / Q000502:physiology*
D000074049:Cytokine TWEAK; D018124:Receptors, Tumor Necrosis Factor; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; C000613299:Tnfrsf12a protein, mouse; D048069:Tumor Necrosis Factors