NLRP3 inflammasome negatively regulates podocyte autophagy in diabetic nephropathy |
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| Affiliation: | 1. College of Basic Medical, Binzhou Medical University, Yantai, Shandong, China;2. Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China;3. The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China;4. Qilu Hospital, Shandong University, Jinan, Shandong, China;5. The Second Hospital of Shandong University, Jinan, Shandong, China;1. Biomedical Engineering Research Center, Kunming Medical University, Kunming 650500, China;2. The Electron Microscopy Laboratory, Kunming Medical University, Kunming 650500, China;3. The Yan''an Hospital Affiliated to Kunming Medical University, Kunming 650051, China;4. The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China;1. Department of Internal Medicine, Asan Institute for Life Science, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea;2. Asan Institute for Life Science, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea;1. Chronic Kidney Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;2. Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece;3. Life Sciences Research Division, Anti-Doping Laboratory Qatar, Sports City Road, Doha, Qatar;4. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;5. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;6. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;1. Department of Pathology, Hebei Medical University, Shijiazhuang, China;2. Hebei Key Laboratory of Kidney Disease, Shijiazhuang, China;3. Hebei Key Laboratory of Animal Science, Shijiazhuang, China |
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| Abstract: | Inflammasome mechanisms are recognized as a key pathophysiology of diabetic nephropathy (DN). The nucleotide-oligomerization domain-like receptor 3 (NLRP3) inflammasome has attracted the most attention. Autophagy as a conserved intracellular catabolic pathway plays essential roles in the maintenance of podocytes. Although autophagy was involved in preventing excessive inflammatory responses in kidney diseases, a clear understanding of the regulation of NLRP3 inflammasome on autophagy in glomerular damage in DN is still lacking. In this study, we focused on the effect of the activation of NLRP3 inflammasome on the suppression of podocyte autophagy and aimed to investigate the role of autophagy in podocyte injury in DN. Podocyte autophagy has been confirmed to be inhibited in high-fat diet/streptozotocin (HFD/STZ)-induced DN mice, and NLRP3 has been found to be upregulated in both mice and human DN biopsies and in vitro. Activation of NLRP3 inflammasome exacerbated podocyte autophagy and reduced podocyte nephrin expression, while silencing of NLRP3 efficiently restored podocyte autophagy and ameliorated podocyte injury induced by high glucose. The results showed that NLRP3 was a negative regulator of autophagy and suggested that restoration of podocyte autophagy by inactivation of NLRP3 under high glucose could reduce podocyte injury. Proper modification of autophagy and inflammasome has the potential to benefit the kidney in DN. |
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| Keywords: | NLRP3 inflammasome Autophagy Inflammation Podocyte Diabetic nephropathy |
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