Figure 2.

Ferroptosis regulates EMT in pulmonary fibrosis via the Nrf2 signaling pathway. Under normal conditions, Keap1 binds to Nrf2, which is degraded by ubiquitination. However, when iron accumulates in epithelial cells, the imbalance between oxidation and antioxidant reaction results in oxidative stress. Nrf2 dissociates from Keap1 during oxidative stress, and Nrf2 enters the nucleus to form heterodimerization with small Maf or Jun proteins. This dimer binds to ARE, transcriptionally activating its target genes and restoring cell homeostasis. Bach1 regulates EMT through CLDN3 and CLDN4, and Bach1 regulates FOXA1 and snail2, forming GRN to regulate EMT. Bach1 decreased the expression of the E-cadherin gene and promoted the occurrence of EMT. Meanwhile, Bach1 directly activates snail2, which promotes EMT by inhibiting cell–cell adhesion. Knockdown of Nrf2 significantly reduces heme oxygenase 1 (HO-1), promotes the accumulation of lipid peroxidation and causes ferroptosis.