FGF20 promotes spinal cord injury repair by inhibiting the formation of necrotic corpuscle P-MLKL/P-RIP1/P-RIP3 in neurons.

The disruption of the local microenvironment subsequent to spinal cord injury (SCI) leads to a substantial loss of neurons in the affected region, which is a major contributing factor to impaired motor function recovery in patients. Fibroblast growth factor 20 (FGF20) is a neurotrophic factor that plays a crucial role in neuronal development and homeostasis. In this study, the recombinant human FGF20 (rhFGF20) was found to mitigate the process of necroptosis in a mouse model of SCI, thereby reducing neural functional deficits and promoting SCI repair. FGF20 protein was injected into the SCI mice via intraperitoneal injection. Using the BMS scale and inclined plane test, we found that FGF20 significantly promoted the recovery of motor function. The Nissl staining revealed the level of neuronal survival within the region of injury. The expression changes of NeuN, GAP43, NF200 and GFAP indicated that FGF20 has the nerve repair ability to delay the formation of glial scar. Through fluorescence detection of Ace-Tubulin and Tyr-Tubulin, FGF20 was revealed to promote the polymerization of axon-regenerated microtubules. Furthermore, FGF20 was also found to reduce the expression levels of necroptosis induced by SCI. These data suggest that FGF20 may exert a neuroprotective effect by inhibiting injury-induced necroptosis, thereby facilitating functional recovery following SCI. Moreover, systemic administration of FGF20 holds promise as a potential therapeutic strategy for repairing the damaged spinal cord. The discovery paves the way for a novel avenue of growth factor research in the field of SCI.