Long-term administration of advanced glycation end-product stimulates the activation of NLRP3 inflammasome and sparking the development of renal injury |
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| Affiliation: | 1. School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan;2. Department of Nutrition, I-Shou University, Kaohsiung, Taiwan;3. Department of Anatomy and Cell Biology, School of Medicine, Taipei Medical University, Taipei, Taiwan;4. Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan;1. Department of Biological Science and Technology, Jinzhong University, Jinzhong 030619, China;2. State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science & Technology, Tianjin 300457, China;3. Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Disease, Department of Nutrition and Food Hygiene, School of Public Health, Medical College of Soochow University, Suzhou 215123, China;4. School of Food & Wine, Ningxia University, Yinchuan 750021, China;5. Department of Agriculture, Hetao College, Inner Mongolia, Bayannur 015000, China;6. College of Chemical Engineering and Material Science, Tianjin University of Science and Technology, Tianjin 300457, China;1. Department of Engineering, University of Cambridge, Cambridge, UK;2. Department of Surgery, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge, UK;3. Wellcome Trust–Medical Research Council Stem Cell Institute, Cambridge Stem Cell Institute, Anne McLaren Laboratory, University of Cambridge, Cambridge, UK;4. Wellcome Trust Sanger Institute, Hinxton, UK;5. Department of Hepatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK |
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| Abstract: | The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys. Results showed that administration of methylglyoxal–bovine serum albumin (MG-BSA) AGE accelerated renal MG, carboxyethyl lysine, carboxymethyl lysine and malondialdehyde formation and, in parallel, the levels of serum creatinine and blood urea nitrogen (BUN) were significantly increased. Expression of RAGE and NLRP3 inflammasome-related proteins (TXNIP, NLRP3, procaspase-1 and caspase-1) and IL (interleukin)-1β secretion were upregulated, whereas the levels of EPCs, eNOS and NO were lower in MG-BSA-treated mice. This induction by MG-BSA was significantly inhibited by RAGE antagonist. Our results firstly reveal a possible mechanism of AGE-mediated renal dysfunction upon NLRP3 inflammasome activation. Therapeutic blockade of RAGE may ameliorate renal and endothelial functions in subjects under high AGE burden. |
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