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Targeting miR-106-3p facilitates functional recovery via inactivating inflammatory microglia and interfering glial scar component deposition after neural injury.

小胶质细胞 基因敲除 脊髓损伤 星形胶质细胞 下调和上调 污渍 体内 胶质瘢痕 基因沉默 脊髓 神经胶质 化学 医学 细胞生物学 病理 炎症 内科学 中枢神经系统 神经科学 生物 生物化学 细胞凋亡 生物技术 基因
作者
Yao‐Hsu Yang,Junqing Zhu
出处
期刊:PubMed 卷期号:23 (20): 9000-9008 被引量:8
标识
DOI:10.26355/eurrev_201910_19300
摘要

The aim of this study was to elucidate whether the knockdown of microRNA-106-3p (miR-106-3p) could mediate the nerve regeneration and functional recovery after the spinal cord injury (SCI) and its potential mechanism.Microglia were extracted from the cerebral cortex of the neonatal rats and cultured in vitro. Subsequently, biomarkers of M1-type and M2-type in microglia transfected with miR-106-3p inhibitor were measured. Furthermore, in vivo SCI model in rats was successfully constructed, and SCI rats were intrathecally injected with miR-106-3p inhibitor or negative control. The expressions of the pro-inflammatory factors in the SCI rats or controls were detected by the enzyme-linked immunosorbent assay (ELISA). The glial scar marker and extracellular matrix were visualized by Western blotting and immunofluorescence, respectively. To observe the nerve function in rats, the movement evaluation was conducted using Basso-Beattie-Bresnahan (BBB) locomotor rating scale.In the inflammatory microglia, miR-106-3p was markedly up-regulated. Western blotting exhibited the downregulation of M1-type cells and the upregulation of M2-type cells after silencing miR-106-3p. In SCI rats, we discovered that the miR-106-3p level in the injured spinal cord was up-regulated within one week following injury. Meanwhile, the levels of the pro-inflammatory factors were significantly reduced in SCI rats with the miR-106-3p knockdown. At 7 days after the injury, the area of the astrocyte scar in the injured spinal cord was remarkably reduced by in vivo knockdown of miR-106-3p. Moreover, the extracellular matrix components secreted in the scar were also significantly inhibited. However, the glial secretion of the neurotrophic factors relatively increased in the SCI rats with the miR-106-3p knockdown. Neurological function recovery was pronounced in SCI rats with the miR-106-3p knockdown relative to controls.The silence of miR-106-3p promotes the recovery of the locomotor function and protects the environment of the neurotization by inactivating inflammatory microglia and reducing the scar formation following SCI.

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