MYCN-mediated pyroptosis and inflammation in the molecular mechanism of MicroRNA-202-3P promote functional recovery in spinal cord injury

作者：Jing Fang, Ke Huang, Guodong Zhang, Bowen Shi, Haidi Bi, Lang Shuai · 发表于：International Immunopharmacology · 年份：2025 · DOI：10.1016/j.intimp.2025.115349 · 研究领域：Spinal Cord Injury Research、Inflammasome and immune disorders、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUND: Spinal cord injury (SCI), which induces severe neurological dysfunction, triggers secondary damage driven primarily by neuroinflammation and pyroptosis. Although microRNA-202-3P (miR-202-3p) is recognized for its regulatory role in inflammatory pathways, its specific involvement in SCI and the underlying mechanisms remain poorly understood. METHODS: A rat SCI model was induced via T10 spinal cord compression, followed by intravenous miR-202-3p administration. Functional recovery was evaluated through the Basso-Beattie-Bresnahan (BBB) score and footprint test. Histopathological changes were evaluated through Hematoxylin and eosin (H&E) staining and Luxol Fast Blue (LFB) Staining. Ultrastructural analysis was performed by transmission electron microscopy (TEM). Immunofluorescence, Western blotting, qPCR, and dual-luciferase assays were used to examine microglial polarization, pyroptosis, and molecular signaling. In vitro, LPS + ATP-stimulated BV-2 microglia were employed to further validate miR-202-3p's effects. Additionally, a co-culture model of BV-2 microglia and VSC4.1 motor neurons was established to assess the neuroprotective effects of miR-202-3p via conditioned media transfer. RESULTS: miR-202-3p treatment significantly improved motor function and bladder control after SCI. It led to M2 microglial polarization, suppression of NLRP3 inflammasome activation, and a reduction in pyroptosis markers. TEM analysis indicated preserved endoplasmic reticulum and mitoc...