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

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.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 reverse-transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, and Western blot.MiR-125b was lowly expressed in SCI-modeled rats. MiR-125b inhibitor 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 mimic did oppositely. MiR-125b inhibitor 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 mimic exerted the opposite effects in SCI-modeled rats and MCM-treated astrocytes.Up-regulation of miR-125b mitigates inflammation, astrocyte activation, and dysfunction in SCI by inactivating the MAPK pathway.©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.

Citation

Xianhu Yue, Mingyong Gu, Tanghong Jia. Upregulated miR-125b mitigates inflammation, astrocyte activation, and dysfunction of spinal cord injury by inactivating the MAPK pathway. Histology and histopathology. 2023 Jan 18:1862418624

PMID: 37166139

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