Mechanism of Hippo/YAP Axis Mediating High Glucose-Induced Ferroptosis in HK-2 Cells

Abstract

The current study focused on the molecular mechanisms behind high glucose (HG)-induced ferroptosis in HK-2 cells. HG-induced epithelial-to-mesenchymal transition (EMT) HK-2 cell model displayed elevated Vimentin, α-SMA, Fe²⁺ and MDA expression, suppressed cell viability and proliferation capabilities, decreased E-cadherin, GPX4 and GSH levels, and increased cell death. Additionally, knockdown of Vimentin or α-SMA caused the opposite outcomes. Restaint of ferroptosis partially reversed the promotion role of knockdown of Vimentin or α-SMA in HK-2 cell proliferation. Further inhibition of the Hippo/YAP pathway could partly regulate the effects of Vimentin or α-SMA on HG-induced ferroptosis and proliferation in HK-2 cells. Conclusively, HG could increase the expression levels of Vimentin and α-SMA in HK-2 cells, and induce EMT, thereby inhibiting the activation of the Hippo/YAP signaling axis and cell proliferation, and promoting cell ferroptosis of HK-2 cells.