Nrf2-mediated chromatin activation of hyperosmotic response genes attenuates heat-induced renal injury [ChIP-seq]

Heat stress can cause whole-body hyperosmolarity and increase risk of chronic kidney disease. Here, we confirmed Nrf2 as the core transcription factor for cellular resistance to hyperosmotic stress through drug screening.

Meanwhile, we constructed a mouse model of renal injury caused by high temperature dehydration, genetic deletion of Nrf2 further increased the renal injury and fibrosis. The natural compound SFN, found in cruciferous plants, can be used to activate Nrf2 and alleviate kidney damage caused by high-temperature dehydration. Mechanistically, we performed hyperosmotic stress in kidney collecting duct cells, and through ATAC-seq and ChIP-seq analysis of multiple histone modifications, found that most of the hyperosmotic response genes changed their chromatin state after pharmacological activation of Nrf2.