HMOX1-mediated ferroptosis participates in gangrenous mastitis in dairy goats.

HMOX1-mediated ferroptosis via mitophagy is a key pathogenic mechanism in caprine gangrenous mastitis.

Gangrenous mastitis is a severe, life-threatening condition in dairy goats caused by bacterial infection, most notably Staphylococcus aureus, and can progress to sepsis and death. Despite its clinical significance, its pathogenesis remains incompletely understood. This study utilized a S. aureus isolate from an affected goat to establish both in vivo and in vitro models, then applied omics sequencing, iron quantification, oxidative stress markers (MDA, GSH, ROS), RT-qPCR, and western blot to investigate ferroptosis—a regulated, iron-dependent form of cell death—as a contributing mechanism. Gene Set Enrichment Analysis (GSEA) identified significant enrichment of the ferroptosis pathway, with heme oxygenase-1 (HMOX1) as the most differentially expressed gene. Gangrenous mammary tissue and infected goat mammary epithelial cells exhibited classic ferroptosis markers: iron accumulation, elevated MDA and ROS, GSH depletion, HMOX1 upregulation, and downregulation of GPX4 and SLC7A11. Administration of ferrostatin-1 (Fer-1) reversed these changes. Upregulation of mitophagy-related proteins (BNIP3, FUNDC1, LC3) was also observed, and inhibition of mitochondrial fission with Mdivi-1 attenuated both mitophagy and ferroptosis. Targeted siRNA knockdown of HMOX1 reduced ferroptosis, mitophagy, and inflammatory responses. These findings establish that HMOX1-driven mitophagy promotes ferroptosis in gangrenous mastitis, offering novel insight into disease pathogenesis and identifying HMOX1 and the ferroptosis pathway as potential therapeutic targets for managing this condition in dairy goats.

This summary was distilled by AI and may occasionally misinterpret data. Confirm critical details with the primary literature before clinical application.