Association between mitophagy and NLRP3 inflammasome in uric acid nephropathy
| Autor: | Xiao-qian Li, Yong-qing Gu, Yuan-yuan Ling, Mei Wang, Jin Miao, Li Xue, Wei Ji, Jun Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Renal Failure, Vol 46, Iss 2 (2024) |
| Druh dokumentu: | article |
| ISSN: | 0886022X 1525-6049 0886-022X |
| DOI: | 10.1080/0886022X.2024.2438847 |
| Popis: | Objective This study was recruited to investigate the role of mitophagy in activating NLRP3 inflammasome in the kidney of uric acid (UA) nephropathy (UAN) rats.Methods This study developed a uric acid nephropathy (UAN) rat model divided into five groups: Negative control (NC), UAN model (M), UAN + autophagy inhibitor (3-MA), UAN + lysosome inhibitor (CQ), and ROS scavenger (N-acetylcysteine, N). H&E staining assessed renal structure, ROS levels were measured with 2, 7-dichlorofluorescin diacetate, and ELISA measured serum markers (creatinine, UA, cystatin C, NGAL, IL-1β, IL-18). Western blot and qRT-PCR evaluated autophagy and inflammation-related protein (LC3 II/I, p62, Pink1, Parkin, NLRP3, Caspase1, IL-1β) expression. NRK-52E cells treated with uric acid and shRNA were analyzed by western blot.Results Renal injury in UAN rats was aggravated by ROS accumulation, which promoted mitophagy and activated the NLRP3 inflammasome. Eliminating ROS reduced mitophagy, inhibited NLRP3 activation, lowered IL-1β and IL-18 levels, and alleviated renal injury. Notably, inhibiting mitophagy increased ROS accumulation, up-regulated NLRP3, Caspase1, and IL-1β expression, further worsening renal injury. In vitro, uric acid treatment of NRK-52E cells altered autophagy-related protein and pro-inflammatory cytokine levels, highlighting the interplay between mitophagy and inflammation in uric acid nephropathy.Conclusion Mitophagy influences renal injury in uric acid nephropathy (UAN) by regulating ROS accumulation and NLRP3 inflammasome activation, suggesting that mitophagy may serve as a potential therapeutic target for UAN. |
| Databáze: | Directory of Open Access Journals |
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