STAT6 Activation Exacerbates Ferroptosis in Airway Epithelium by Inhibiting PRKN-Mediated Mitophagy in Pulmonary Fibrosis.

ABSTRACT: Pulmonary fibrosis (PF) remains a clinically intractable condition with limited therapies. Ferroptosis has emerged as a critical driver of PF. The previous study demonstrates that increased secretion of tissue plasminogen activator from ferroptotic airway epithelial cells contributes to PF progression in a paracrine manner. Herein, the indispensable role of signal transducer and activator of transduction 6 (STAT6) is further elucidated in maintaining airway epithelial homeostasis during PF and uncovers a novel mechanism by which STAT6 regulates mitophagy to modulate ferroptosis. Specifically, mitophagy is induced during PF along with STAT6 activation, and deficiency of STAT6 significantly alleviates epithelial ferroptosis and PF. Mechanistically, STAT6 directly binds to the parkin RBR E3 u

SUBMITTER: Yang Y 

PROVIDER: S-EPMC12520474 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature