The NLPR3 Inflammasome and Obesity-related Kidney Disease

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2017 Sep 1

PMID 28857469

Citations 26

Authors

Ben Ke

Wen Shen

Xiangdong Fang

Qinghua Wu

Affiliations

Soon will be listed here.

Abstract

Over the past decade, the prevalence of obesity has increased, accompanied by a parallel increase in the prevalence of chronic kidney disease (CKD). Mounting evidence suggests that high body mass index (BMI) and obesity are important risk factors for CKD, but little is known about the mechanisms of obesity-related kidney disease (ORKD). The NLRP3 inflammasome is a polyprotein complex that plays a crucial role in the inflammatory process, and numerous recent studies suggest that the NLRP3 inflammasome is involved in ORKD development and may serve as a key modulator of ORKD. Moreover, inhibiting activation of the NLRP3 inflammasome has been shown to attenuate ORKD. In this review, we summarize recent progress in understanding the link between the NLRP3 inflammasome and ORKD and discuss targeting the NLRP3 inflammasome as a novel therapeutic approach for ORKD.

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References

Granata S, Dalla Gassa A, Tomei P, Lupo A, Zaza G . Mitochondria: a new therapeutic target in chronic kidney disease. Nutr Metab (Lond). 2015; 12:49. PMC: 4660721. DOI: 10.1186/s12986-015-0044-z. View

Bochud M, Nussberger J, Bovet P, Maillard M, Elston R, Paccaud F . Plasma aldosterone is independently associated with the metabolic syndrome. Hypertension. 2006; 48(2):239-45. DOI: 10.1161/01.HYP.0000231338.41548.fc. View

Lee E, Kim H, Kang J, Lee E, Yadav D, Kwon M . Oleanolic acid and N-acetylcysteine ameliorate diabetic nephropathy through reduction of oxidative stress and endoplasmic reticulum stress in a type 2 diabetic rat model. Nephrol Dial Transplant. 2015; 31(3):391-400. DOI: 10.1093/ndt/gfv377. View

Hotamisligil G, Shargill N, Spiegelman B . Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993; 259(5091):87-91. DOI: 10.1126/science.7678183. View

Wang C, Wu M, Arvapalli R, Dai X, Mahmood M, Driscoll H . Acetaminophen attenuates obesity-related renal injury through ER-mediated stress mechanisms. Cell Physiol Biochem. 2014; 33(4):1139-48. DOI: 10.1159/000358683. View

Ruster C, Wolf G . The role of the renin-angiotensin-aldosterone system in obesity-related renal diseases. Semin Nephrol. 2013; 33(1):44-53. DOI: 10.1016/j.semnephrol.2012.12.002. View

Altshuler-Keylin S, Kajimura S . Mitochondrial homeostasis in adipose tissue remodeling. Sci Signal. 2017; 10(468). PMC: 5465966. DOI: 10.1126/scisignal.aai9248. View

Che R, Yuan Y, Huang S, Zhang A . Mitochondrial dysfunction in the pathophysiology of renal diseases. Am J Physiol Renal Physiol. 2013; 306(4):F367-78. DOI: 10.1152/ajprenal.00571.2013. View

Chung H, Vilaysane A, Lau A, Stahl M, Morampudi V, Bondzi-Simpson A . NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis. Cell Death Differ. 2016; 23(8):1331-46. PMC: 4947664. DOI: 10.1038/cdd.2016.14. View

10.

Chen W, Wang J, Luo Y, Wang T, Li X, Li A . Ginsenoside Rb1 and compound K improve insulin signaling and inhibit ER stress-associated NLRP3 inflammasome activation in adipose tissue. J Ginseng Res. 2016; 40(4):351-358. PMC: 5052408. DOI: 10.1016/j.jgr.2015.11.002. View

11.

Zhao Y, Li Q, Zhao W, Li J, Sun Y, Liu K . Astragaloside IV and cycloastragenol are equally effective in inhibition of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in the endothelium. J Ethnopharmacol. 2015; 169:210-8. DOI: 10.1016/j.jep.2015.04.030. View

12.

Vivante A, Golan E, Tzur D, Leiba A, Tirosh A, Skorecki K . Body mass index in 1.2 million adolescents and risk for end-stage renal disease. Arch Intern Med. 2012; 172(21):1644-50. PMC: 4941233. DOI: 10.1001/2013.jamainternmed.85. View

13.

Ding W, Xu C, Wang B, Zhang M . Rotenone Attenuates Renal Injury in Aldosterone-Infused Rats by Inhibiting Oxidative Stress, Mitochondrial Dysfunction, and Inflammasome Activation. Med Sci Monit. 2015; 21:3136-43. PMC: 4614375. DOI: 10.12659/msm.895945. View

14.

He X, Guan B, Zhu L . Hemodynamics as Measured With Color Doppler Sonography in Early-Stage Obesity-Related Nephropathy in Children. J Ultrasound Med. 2017; 36(8):1671-1677. DOI: 10.7863/ultra.16.04025. View

15.

Mohamed I, Hafez S, Fairaq A, Ergul A, Imig J, El-Remessy A . Thioredoxin-interacting protein is required for endothelial NLRP3 inflammasome activation and cell death in a rat model of high-fat diet. Diabetologia. 2013; 57(2):413-23. PMC: 3947289. DOI: 10.1007/s00125-013-3101-z. View

16.

Li A, Zhang S, Li J, Liu K, Huang F, Liu B . Metformin and resveratrol inhibit Drp1-mediated mitochondrial fission and prevent ER stress-associated NLRP3 inflammasome activation in the adipose tissue of diabetic mice. Mol Cell Endocrinol. 2016; 434:36-47. DOI: 10.1016/j.mce.2016.06.008. View

17.

DAgati V, Chagnac A, de Vries A, Levi M, Porrini E, Herman-Edelstein M . Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat Rev Nephrol. 2016; 12(8):453-71. DOI: 10.1038/nrneph.2016.75. View

18.

Vallon V, Thomson S . Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2016; 60(2):215-225. PMC: 5884445. DOI: 10.1007/s00125-016-4157-3. View

19.

Chen H, Yang D, Han F, Tan J, Zhang L, Xiao J . The Bacterial T6SS Effector EvpP Prevents NLRP3 Inflammasome Activation by Inhibiting the Ca-Dependent MAPK-Jnk Pathway. Cell Host Microbe. 2017; 21(1):47-58. DOI: 10.1016/j.chom.2016.12.004. View

20.

Ding W, Guo H, Xu C, Wang B, Zhang M, Ding F . Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury. Oncotarget. 2016; 7(14):17479-91. PMC: 4951227. DOI: 10.18632/oncotarget.8243. View