[Mechanistic study on TFEB nuclear translocation-mediated lysosomal degradation of GPX4 promoting ferroptosis in trophoblast cells in pre-eclampsia].

levels, ROS fluorescence intensity, LDH release, and MDA level were markedly increased, while SOD activity and GSH levels were significantly decreased. TFEB and p-TFEB protein expression showed significant up-regulation, whereas GPX4 protein expression was notably down-regulated. TFEB nuclear translocation occurred with enhanced lysosomal fluorescence intensity. Compared with the hypoxia+si-NC group, the hypoxia+si-TFEB group demonstrated significantly increased viability, invasion number, and migration rate of cells, accompanied by reduced ferroptosis levels. TFEB nuclear translocation was inhibited, and lysosomal fluorescence intensity decreased. Compared with the hypoxia+si-TFEB group, ferroptosis-related indicators in HTR8-S/Vneo cells were reversed in the hypoxia+si-TFEB+RSL3 group. In contrast, the cellular ferroptosis level was elevated in the hypoxia+si-TFEB+PP242 group. Conclusion Inhibition of TFEB nuclear translocation reduces ferroptosis in human embryonic trophoblast cells HTR8-S/Vneo, possibly by suppressing the lysosomal degradation of GPX4.