Dioscin regulates oxidative stress and autophagy in uric acid-induced HK-2 cells through the P62-KEAP1-NRF2 signaling pathway.

OBJECTIVE

This study aims to explore the therapeutic effects and mechanisms of dioscin on the UA-induced HK-2 cells fibrosis model by modulating oxidative stress and autophagy.

METHODS

HK-2 cells fibrosis was constructed by UA stimulation. CCK8 was used to assess cell proliferation. Flow cytometry was employed to detect apoptosis. MDC staining was performed to observe the formation of autophagosomes. Western blot was used to evaluate the levels of oxidative stress, autophagy and fibrosis markers. The detection of ROS and Elisa assay were used to analyze the changes of oxidative stress.

RESULTS

Dioscin significantly inhibits cell apoptosis. Dioscin increases the expression of LC3, Beclin-1 and NRF2 and decreases the expression of P62 and KEAP1. Furthermore, dioscin inhibits the levels of ROS and MDA, and promotes the levels of SOD and CAT. Moreover, dioscin significantly downregulates the expression of TGF-β, FN, and Collagen I. However, the regulatory effects of dioscin on these indicators are inhibited when NRF2 is knocked down.

CONCLUSION

These results suggest that dioscin treats the UA-induced HK-2 cells fibrosis model by targeting the modulation of NRF2 to regulate oxidative stress and promote protective autophagy. The mechanism may be associated with the restoration of the P62-KEAP1-NRF2 signaling pathway.

TRIAL REGISTRATION

Not applicable.