Upregulated miR-125b mitigates inflammation, astrocyte activation, and dysfunction of spinal cord injury by inactivating the MAPK pathway

• Xianhu Yue ^[1] ; Mingyong Gu ^[1] ; Tanghong Jia ^[1]
  1. [1] Shandong University

     Shandong University

     China

     
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 39, Nº. 2, 2024, págs. 225-237
• Idioma: inglés
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• Resumen

  • y. Background. Since the abnormal expression of miR-125b in spinal cord injury (SCI) and the regulatory effect of miR-125b on the MAPK pathway have been expounded, we attempt to investigate whether miR-125b exerts a regulatory effect on SCI by modulating the MAPK pathway.

    Method. A SCI rat model was established. The rats were treated with miR-125b antagomir or agomir, and their motor function affected by miR-125b was further detected by Basso-Beattie-Bresnahan (BBB) scoring.

    The histopathological changes and neuronal loss in the spinal cord were evaluated using hematoxylin-eosin and Nissl staining. Microglia-conditioned medium (MCM) was prepared and further used to treat the astrocytes, the activation of which was evaluated via immunofluorescence staining. The expressions of miR-125b, inflammation-related factors (IL-6, IL-1β, TNF-α, and IL-10), and MAPK pathway-related proteins (p38, ERK1/2, and JNK1/2 as well as their phosphorylated (p) forms) in the spinal cord, serum, and MCM-treated astrocytes of rats were determined by reversetranscription quantitative polymerase chain reaction (RTqPCR), enzyme-linked immunosorbent assay, and Western blot.

    Result. MiR-125b was lowly expressed in SCImodeled rats. MiR-125b downregulation aggravated the impaired motor function, the disorder within the tissue, astrocyte activation, and neuron loss in the spinal cord tissues of SCI-modeled rats, while miR-125b upregulation did oppositely. MiR-125b downregulation enhanced the levels of IL-6, IL-1β, TNF-α, p38, p-p38, p-ERK1/2, and p-JNK1/2, whilst reducing that of IL-10.

    Contrarily, miR-125b upregulation exerted the opposite effects in SCI-modeled rats and MCM-treated astrocytes.

    Conclusion. Up-regulation of miR-125b mitigates inflammation, astrocyte activation, and dysfunction in SCI by inactivating the MAPK pathway.