Attenuates Inflammation in Diabetes-Induced Kidney Injury by Targeting NLRP3 Inflammasome

Abstract

Background: In recent years, with the increasing prevalence of diabetes, diabetic nepropathy (DN) has become a serious public health threat. This study investigated the potential role of Nlr family member X1 (NLRX1) in DN and the underlying mechanisms. Methods: Diabetic model of mice were injected intraperitoneally (i.p.) with streptozotocin, and fed with the high fat diet (HFD) as the in vivo model of diabetes-induced kidney injury. Rat mesangial cells (MCs) were exposed with high glucose (30 mmol/L glucose) as in vitro cell model. Results: NLRX1 mRNA (messenger ribonucleic acid) and protein levels were down-regulated in the kidney tissue of diabetic mouse model of kidney injury. NLRX1 protein administration reduced inflammation and prevented kidney injury in the mouse model. NLRX1 inactivated NOD-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome in both the mouse model and in vitro cell model. Further experiments showed that the administration of NLRP3 attenuated the effects of NLRX1 on inflammation of diabetes-induced kidney injury model. Conclusions: In conclusion, NLRX1 attenuates the inflammation in diabetes-induced kidney injury by inhibiting NLRP3 inflammasome, which may serve as be a potent target for preventing the progression of DN through inhibition of NLRP3 inflammasome-dependent inflammation.