Integrated analysis of autophagy and ferroptosis mediating aristolochic acid A-induced nephrotoxicity via transcriptome and m6A epigenetic transcriptome in HK-2 cells.

AAA induces oxidative stress, autophagy, and ferroptosis in HK-2 cells, with m6A methylation alterations closely linked to these processes and involving IGF2BP2 as a key mediator.

• Why it matters: Understanding the epigenetic mechanisms underlying AAA-induced nephrotoxicity is crucial because AAA causes irreversible renal damage and tumors, yet its molecular pathways remain unclear.
• What they did: The study treated HK-2 cells with AAA and used mRNA-seq and MeRIP-seq to identify differentially expressed genes and m6A methylation changes, focusing on oxidative stress, autophagy, and ferroptosis pathways, with validation experiments highlighting IGF2BP2's role.
• The result: Findings reveal that AAA-triggered renal cell damage involves altered m6A methylation and dysregulation of related genes, especially IGF2BP2, suggesting an epigenetic mechanism that may inform future therapeutic strategies.