Association between mitophagy and inflammasome in uric acid nephropathy.

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, 7dichlorofluorescin diacetate, and ELISA measured serum markers (, , cystatin , , , ). Western blot and qRT-PCR evaluated autophagy and inflammation-related protein (, , , , , , ) 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 inflammasome. Eliminating ROS reduced mitophagy, inhibited NLRP3 activation, lowered and levels, and alleviated renal injury. Notably, inhibiting mitophagy increased ROS accumulation, up-regulated , , and 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 inflammasome activation, suggesting that mitophagy may serve as a potential therapeutic target for UAN.