Guanine-rich RNA sequence binding factor 1 regulates neuronal ferroptosis after spinal cord injury in rats via the GPX4 signaling pathway.

Spinal cord injury (SCI) can trigger multiple forms of neuronal cell death. Among these, ferroptosis stands out as a particularly important style of cell death due to its iron overload-dependent lipid peroxidative regulatory mechanism. The guanine-rich RNA sequence binding factor 1 (GRSF1) is an RNA-binding protein that has been implicated in cellular senescence, mitochondrial function, oxidative stress, erythropoiesis, and embryonic brain development. However, the function of GRSF1 in neuronal ferroptosis after SCI remains unclear. Here, we established a SCI rat model in vivo and evaluated the function of GRSF1 on neuronal ferroptosis by inhibiting and overexpressing GRSF1. We firstly verified the protein expression of GRSF1 and GPX4 at different time points after SCI. According of changes in expression, we chose 3 d post SCI to assess the effect of GRSF1 on ferroptosis. We found that GRSF1 expression decreased after SCI. In addition, GRSF1 was mainly localized in the cytoplasm of neurons. The results also showed that overexpression of GRSF1 promoted recovery of neurological functional after SCI. Further investigation revealed that GRSF1 might attenuate neuronal ferroptosis by regulating the GPX4 protein expression levels. In summary, our findings indicate that GRSF1 attenuates injury in SCI and reduces neuron ferroptosis and promotes functional recovery via GPX4.