[Frontiers in Bioscience 13, 580-589, January 1, 2008]

TWEAKing renal injury

Ana Belen Sanz1, Juan Antonio Moreno1, Maria Dolores Sanchez-Nino1, Alvaro C Ucero1, Alberto Benito1, Beatriz Santamaria1, Pilar Justo1, M. Concepcion Izquierdo1, Jesus Egido1,2, Luis Miguel Blanco-Colio1, Alberto Ortiz1,2

1Fundacion Jimenez Diaz, Universidad Autonoma de Madrid, 2040 Madrid, Spain, 2Fundacion Renal Inigo Alvarez de Toledo, Madrid, Spain


1. Abstract
2. Introduction
3. TWEAK and Fn14
3.1. Structure
3.2. Expression
3.3. Signaling pathway
4. TWEAK biological activity
5. TWEAK and cell death
6. The role of TWEAK and Fn14 in renal injury
6.1. Glomerular injury
6.2. Acute kidney injury
7. The way forward
8. Acknowledgment
9. References


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.