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Updated: Jun 5, 2025

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Association between mitophagy and NLRP3 inflammasome in uric acid nephropathy
Xiao-Qian Li1, Yong-Qing Gu2, Yuan-Yuan Ling3
1Department of Nephrology, Nantong Hospital to Nanjing University of Chinese Medicine, Nantong Hospital of Traditional Chinese Medicine, Nantong, Jiangsu, China.
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.
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