晚期糖基化终末产物受体在晚期氧化蛋白产物诱导性足细胞凋亡中起着主要作用

Nie, J.; Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, China; email:niejing@fimmu.com

The accumulation of plasma advanced oxidation protein products (AOPPs) is prevalent in chronic kidney disease. We previously showed that accumulation of AOPPs resulted in podocyte apoptosis and their deletion by a cascade of signaling events coupled with intracellular oxidative stress. The transmembrane receptor that specifically transmits the AOPPs' signals to elicit cellular activity, however, remains unknown. Using co-immunoprecipitation and immunofluorescence, we found that AOPPs colocalized and interacted with the receptor of advanced glycation end products (RAGE) on podocytes. Blocking RAGE by anti-RAGE immunoglobulin G or its silencing by siRNA significantly protected podocytes from AOPPs-induced apoptosis both in vitro and in vivo and ameliorated albuminuria in AOPPs-challenged mice. AOPPs-induced activation of nicotinamide adenine dinucleotide phosphate oxidase and the excessive generation of intracellular superoxide were largely inhibited by anti-RAGE immunoglobulin G or RAGE siRNA. Moreover, blockade of RAGE decreased the activation of the p53/Bax/caspase-dependent proapoptotic pathway induced by AOPPs. Thus, AOPPs interact with RAGE to induce podocyte apoptosis and this, in part, may contribute to the progression of chronic kidney disease. © 2012 International Society of Nephrology.

Key Lab for Organ Failure Research, Ministry of Education, Nanfang Hospital, Guangzhou, China