Role of sweet taste receptors in the activation of NLRP3 inflammasome signaling in diabetic kidney disease

Abstract

Objective To investigate the role of sweet taste receptors(STRs)in the activation of reactive oxygen species (ROS)-NLRP3 inflammasome signaling in diabetic kidney disease(DKD). Methods DKD mouse were established by high-fat diet and streptozotocin. After mouse glomerular mesangial cells(GMCs)were exposed to high glucose, STRs(T1R2/T1R3)and associated signaling components and NLRP3 inflammasome signaling components expressions were detected. After GMCs were treated with STRs inhibitor lactisole, the production of ROS was detected and the role of STRs in the activation of NLRP3 signaling was investigated. Results Under high glucose condition, the expressions of T1R2, T1R3, Gα-gustducin, phospholipase C-β2, and TRPM5 were significantly decreased in vivo and in vitro(all P<0.05)and ROS-NLRP3 signaling was activated(all P<0.05). Lactisole significantly mitigated the production of ROS and the activation of NLRP3 inflammasome signaling stimulated by high glucose in GMCs(all P<0.05). Conclusion The STRs(T1R2/T1R3)-mediated signaling pathway may be involved in the regulation of ROS-NLRP3 inflammatory signaling, suggesting that STRs may act as new therapeutic targets of DKD. (Chin J Endocrinol Metab, 2018, 34: 587-593) Key words: Sweet taste receptors; Reactive oxygen species; NLRP3 inflammasome; Diabetic kidney disease