Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
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.