The spatiotemporal and paradoxical roles of NRF2 in renal toxicity and kidney diseases.

Over 10% of the global population is at risk to kidney disorders. Nuclear factor erythroid-derived 2-related factor 2 (NRF2), a pivotal regulator of redox homeostasis, orchestrates antioxidant response that effectively counters oxidative stress and inflammatory response in a variety of acute pathophysiological conditions, including acute kidney injury (AKI) and early stage of renal toxicity. However, if persistently activated, NRF2-induced transcriptional cascade may disrupt normal cell signaling and contribute to numerous chronic pathogenic processes such as fibrosis.

Nrf2 protects against renal fibrosis induced by chronic cadmium exposure in mice.

Environmental cadmium (Cd) exposure is a serious public health concern, as the kidney is the primary target for Cd exposure. The present study aimed to investigate the role and underlying mechanisms of nuclear factor erythroid-derived 2-like 2 (Nrf2) in renal fibrosis induced by chronic Cd exposure. Nrf2 knockout (Nrf2-KO) mice and their wild-type littermates (Nrf2-WT) were exposed to 100 or 200 ppm Cd in drinking water for up to 16 or 24 weeks.