FGF5 alleviates ferroptosis in renal tubular epithelial cells by inducing mitophagy under in vitro ischemia-reperfusion-like injury.

Renal ischemic disease represents a severe clinical pathological condition commonly observed in acute kidney injury (AKI), renal transplantation, and kidney surgery. It leads to renal tubular epithelial cell damage, inflammatory responses, and cell death, potentially progressing to chronic kidney disease (CKD) or even renal failure, significantly impairing patients' quality of life and survival rates. Current therapeutic strategies for renal ischemia-reperfusion injury (IRI) include pharmacological interventions, cell therapy, and gene therapy, yet their efficacy remains limited and may be accompanied by adverse effects. Thus, there is an urgent need to explore novel therapeutic targets and strategies. Fibroblast growth factor 5 (FGF5), a key member of the FGF family, plays crucial roles in cell proliferation, differentiation, and tissue repair. However, its specific mechanism in renal IRI remains unclear. This study aimed to investigate the therapeutic effects of FGF5 on renal IRI and its underlying molecular mechanisms in vitro. Using normal rat kidney-52E (NRK-52E) and human kidney-2 (HK-2 cell) models, we evaluated the impact of FGF5 on cell viability, oxidative stress, inflammatory responses, and renal cell death. Our findings demonstrate that FGF5 exhibits significant biological activity and further reveal its regulatory role in suppressing ferroptosis through activation of the Mitophagy. In conclusion, this study identifies FGF5 as a potential therapeutic agent for renal IRI and provides a theoretical foundation for developing FGF5-based treatment strategies. These findings hold substantial scientific and clinical value, potentially opening new avenues for treating renal ischemic diseases.