In summary, NRF2 may be a hub of P62-KEAP1-NRF2, it is also the target spot of dioscin in curing UA induced-HK-2 cells fibrosis model, knocking down NRF2 interrupted the protective mechanism of dioscin in UA induced-HK-2 cells fibrosis model, eliminates the ability in activating autophagy, resisting oxidative stress and anti-fibrosis (Fig. 6). Here, KEAP1 is linked to fibrosis.