Activation of NRF2 Signaling Pathway Delays the Progression of Hyperuricemic Nephropathy by Reducing Oxidative Stress.

ABSTRACT: Hyperuricemia (HUA)-induced oxidative stress is a crucial contributor to hyperuricemic nephropathy (HN), but the molecular mechanisms underlying the disturbed redox homeostasis in kidneys remain elusive. Using RNA sequencing, together with biochemical analyses, we found that nuclear factor erythroid 2-related factor 2 (NRF2) expression and nuclear localization levels were increased in early HN progression and then gradually declined below the baseline level. We identified the impaired activity of the NRF2-activated antioxidant pathway as a driver of oxidative damage in HN progression. Through nrf2 deletion, we further confirmed aggravated kidney damage in nrf2 knockout HN mice compared with HN mice. In contrast, the pharmacological agonist of NRF2 improved kidney function and

SUBMITTER: Qiao P 

PROVIDER: S-EPMC10215166 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature