Scholarlink

<p>Degenerative cervical myelopathy (DCM) is a progressive spinal cord disorder primarily caused by chronic cervical compression. While Sortilin is implicated in degenerative and neuroinflammatory diseases, its specific role in DCM remains unclear. This study investigated the Sortilin-progranulin (PGRN) axis in DCM pathogenesis, and its potential association with endoplasmic reticulum (ER) stress, microglial activation and motor neuron injury. We established an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model in BV2 microglia and an in vivo rat chronic compression DCM model. Sortilin expression was modulated via AAV-mediated shRNA knockdown (sh-Sortilin) or overexpression (OE-Sortilin) in vivo, and siRNA interference in vitro. We assessed cell viability, apoptosis and ROS production via CCK-8 and flow cytometry, performed immunofluorescence with quantitative Pearson’s correlation analysis, and examined neurological function, histopathology, apoptosis and microglial activation in DCM rats. Protein levels of ER stress markers, microglial activation markers and PGRN were detected by western blot, and serum pro-inflammatory cytokines via ELISA. Sortilin knockdown was associated with improved cell viability, as well as reduced apoptosis, ROS production, ER stress and pro-inflammatory activation in OGD/R-injured BV2 cells. PGRN knockdown reversed the protective effects of Sortilin silencing. In DCM rats, sh-Sortilin treatment was associated with improved neurological scores, reduced tissue damage and neuronal apoptosis, suppressed microglial activation and neuroinflammation, restored PGRN expression, and downregulated ER stress marker levels, while OE-Sortilin treatment showed opposite associations with DCM pathology and functional outcomes. In conclusion, the beneficial effects of Sortilin knockdown on DCM-related phenotypes are closely linked to PGRN, potentially via attenuating microglial ER stress and pro-inflammatory activation to protect spinal motor neurons.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Sortilin is Associated with PGRN-Mediated Endoplasmic Reticulum Stress and Activation of Microglia in a Rat Model of Degenerative Cervical Myelopathy

  • 期刊论文

  • 发表日期：

    2026年4月25日

查看全文
  • Linkai Lei,
  • Xinping Wang,
  • Jianfeng Zhang,
  • Jijuan Zhao

摘要

Degenerative cervical myelopathy (DCM) is a progressive spinal cord disorder primarily caused by chronic cervical compression. While Sortilin is implicated in degenerative and neuroinflammatory diseases, its specific role in DCM remains unclear. This study investigated the Sortilin-progranulin (PGRN) axis in DCM pathogenesis, and its potential association with endoplasmic reticulum (ER) stress, microglial activation and motor neuron injury. We established an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model in BV2 microglia and an in vivo rat chronic compression DCM model. Sortilin expression was modulated via AAV-mediated shRNA knockdown (sh-Sortilin) or overexpression (OE-Sortilin) in vivo, and siRNA interference in vitro. We assessed cell viability, apoptosis and ROS production via CCK-8 and flow cytometry, performed immunofluorescence with quantitative Pearson’s correlation analysis, and examined neurological function, histopathology, apoptosis and microglial activation in DCM rats. Protein levels of ER stress markers, microglial activation markers and PGRN were detected by western blot, and serum pro-inflammatory cytokines via ELISA. Sortilin knockdown was associated with improved cell viability, as well as reduced apoptosis, ROS production, ER stress and pro-inflammatory activation in OGD/R-injured BV2 cells. PGRN knockdown reversed the protective effects of Sortilin silencing. In DCM rats, sh-Sortilin treatment was associated with improved neurological scores, reduced tissue damage and neuronal apoptosis, suppressed microglial activation and neuroinflammation, restored PGRN expression, and downregulated ER stress marker levels, while OE-Sortilin treatment showed opposite associations with DCM pathology and functional outcomes. In conclusion, the beneficial effects of Sortilin knockdown on DCM-related phenotypes are closely linked to PGRN, potentially via attenuating microglial ER stress and pro-inflammatory activation to protect spinal motor neurons.

Graphical Abstract