[Frontiers in Bioscience 14, 3740-3749, January 1, 2009]

[Frontiers in Bioscience 14, 3740-3749, January 1, 2009]

Trail and kidney disease

Corina Lorz^1,2, Alberto Benito¹, Alvaro C. Ucero¹, Beatriz Santamaría¹, Alberto Ortiz¹

1 Renal and Vascular Research Laboratory, Fundacion Jimenez Diaz-UAM, Madrid, Spain,²Current address: Basic Research Department, Epithelial Biomedicine Division, Molecular Oncology Unit, Ciemat, Madrid, Spain.

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The TRAIL/TRAIL-receptor system: 3.1. The TRAIL cytokine; 3.2. TRAIL receptors; 3.3. TRAIL signalling pathways
4. Expression of TRAIL and its receptors in the kidney: 4.1. Healthy kidney; 4.2. Diseased kidney; 4.3. OPG: friend or foe?
5. Perspectives
6. References

1. ABSTRACT

TNF-related apoptosis-inducing ligand (TRAIL, TNFSF10) is a cytokine belonging to the TNF superfamily that has been recently linked to the pathogenesis of diabetic nephropathy. TRAIL may modulate cell survival and proliferation through interaction with two different receptors, TRAIL-R1 and TRAIL-R2, and the actions of TRAIL are regulated by three decoy receptors, TRAIL-R3, TRAIL-R4 and osteoprotegerin. Both TRAIL and their receptors are expressed by renal cells. In diabetic nephropathy the glomerular and tubulointerstitial expression of TRAIL is increased, and in tubular cells proinflammatory cytokines enhance TRAIL expression. Additionally, a high glucose microenvironment sensitizes tubular cells to apoptosis induced by TRAIL. Renal expression of OPG is increased in diabetic nephropathy and OPG counteracts the actions of TRAIL in cultured cells. Overall these data point to a role of TRAIL in the pathogenesis of diabetic nephropathy through interactions with other cytokines and hyperglycemia.