Figure 10.

Mechanisms by which the activation of NRF2 signaling ameliorates kidney injury in HN mice. Under physiological conditions, cells produce an appropriate amount of ROS to adapt to normal physiological activities, while NRF2 exists in the cytoplasm at a lower level. High levels of UA will be transported into cells by transporters on the apical membrane of renal tubular epithelial cells, stimulating NOX4 to produce excessive ROS. Excessive ROS causes mitochondrial fusion and fission disorders, leading to mitochondrial dysfunction. Damaged mitochondria produce excessive mitochondrial ROS and aggravate cellular oxidative stress. The administration of NRF2 agonist sulforaphane (SFN) can improve cellular oxidative stress by down-regulating NOX4 expression and remodeling mitochondrial homeostasis. Moreover, NRF2 activation enhances the antioxidant capacity of cells by upregulating the expression of HO-1/NQO1, reduces renal fibrosis by downregulating the expression of TGF-β1/α-SMA/Collagen 1, and ultimately improves renal function and slows down disease progression.