Knockdown of Secreted Phosphoprotein 1 Inhibits Pyroptosis and IL-17 Signaling Pathway to Alleviate Epilepsy Progression

Epilepsy is a severe central Nervous System Disorder. This study aims to investigate the role of secreted phosphoprotein 1 (SPP1) in epilepsy. GSE88992 and GSE73878 datasets were used for bioinformatics analysis to screen hub genes in epilepsy. SPP1 was identified by aprotein-protein interaction network. In vitro, knockdown of SPP1 promoted cell proliferation, suppressed Apoptosis, inflammation, and Pyroptosis in lipopolysaccharide induced BV2 cells. Epilepsy rat model was successfully constructed by intraperitoneal injection of pilocarpine, with the increased seizure scores, seizure durations, and decreased latency to seizure. Hematoxylin-eosinand Nissl staining results exhibited neuronal damage to hippocampal tissue in epilepsy rats, and knockdown of SPP1 reduced neuronal damage and alleviated the onset of epilepsy. Furthermore, silencing SPP1 suppressed inflammation and Pyroptosis in vivo. Interleukin (IL)-17 pathway was identified as the downstream pathway of SPP1, and knockdown of SPP1 restrained the IL-17 pathway in vitro. Collectively, inhibition of SPP1 suppresses Pyroptosis and IL-17signaling pathway, thereby alleviating epilepsy development.

IL‐17 pathway; SPP1; bioinformatics analysis; epilepsy; pyroptosis.