The mechanism by which transcription factors regulate ferroptosis in diabetic complications and its therapeutic potential

Transcription factors (TFs) are central regulators of ferroptosis, an iron‑dependent lipid peroxidation‑driven cell death, in diabetic complications. This review synthesizes evidence into an integrated network model in whHIF-1αich a pro‑survival arm (NRF2) and a pro‑ferroptotic arm (HIF‑1α, p53, ATF4) antagonistically control iron metabolism, antioxidant defense, and lipid peroxidation. These TF networks crosstalk with autophagy and apoptosis via ATF4‑CHOP and p53 pathways, and are modulated by epigenetic mechanisms. Targeting these axes with KEAP1‑NRF2 inhibitors, PROTACs, or ncRNA‑based therapies shows promise, but clinical translation faces challenges due to TF pleiotropy, lack of cell‑type specificity, and absence of clinical ferroptosis biomarkers.