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Increased expression of miR142 and miR155 in glial and immune cells after traumatic brain injury may contribute to neuroinflammation via astrocyte activation.
Brain Pathology ( IF 6.4 ) Pub Date : 2020-05-27 , DOI: 10.1111/bpa.12865
Anatoly Korotkov 1 , Noora Puhakka 2 , Shalini Das Gupta 2 , Niina Vuokila 2 , Diede W M Broekaart 1 , Jasper J Anink 1 , Mette Heiskanen 2 , Jenni Karttunen 2 , Jackelien van Scheppingen 1, 3 , Inge Huitinga 3 , James D Mills 1 , Erwin A van Vliet 1, 4 , Asla Pitkänen 2 , Eleonora Aronica 1, 5
Affiliation  

Traumatic brain injury (TBI) is associated with the pathological activation of immune‐competent cells in the brain, such as astrocytes, microglia and infiltrating immune blood cells, resulting in chronic inflammation and gliosis. This may contribute to the secondary injury after TBI, thus understanding of these processes is crucial for the development of effective treatments of post‐traumatic pathologies. MicroRNAs (miRNAs, miRs) are small noncoding RNAs, functioning as posttranscriptional regulators of gene expression. The increased expression of inflammation‐associated microRNAs miR155 and miR142 has been reported after TBI in rats. However, expression of these miRNAs in the human brain post‐TBI is not studied and their functions are not well understood. Moreover, circulating miR155 and miR142 are candidate biomarkers. Therefore, we characterized miR142 and miR155 expression in the perilesional cortex and plasma of rats that underwent lateral fluid‐percussion injury, a model for TBI and in the human perilesional cortex post‐TBI. We demonstrated higher miR155 and miR142 expression in the perilesional cortex of rats 2 weeks post‐TBI. In plasma, miR155 was associated with proteins and miR142 with extracellular vesicles, however their expression did not change. In the human perilesional cortex miR155 was most prominently expressed by activated astrocytes, whereas miR142 was expressed predominantly by microglia, macrophages and lymphocytes. Pro‐inflammatory medium from macrophage‐like cells stimulated miR155 expression in astrocytes and overexpression of miR142 in these cells further potentiated a pro‐inflammatory state of activated astrocytes. We conclude that miR155 and miR142 promote brain inflammation via astrocyte activation and may be involved in the secondary brain injury after TBI.

中文翻译:

创伤性脑损伤后胶质细胞和免疫细胞中 miR142 和 miR155 的表达增加可能通过星形胶质细胞活化导致神经炎症。

创伤性脑损伤(TBI)与大脑中免疫活性细胞的病理激活有关,如星形胶质细胞、小胶质细胞和浸润性免疫血细胞,导致慢性炎症和神经胶质增生。这可能会导致 TBI 后的继发性损伤,因此了解这些过程对于开发有效的创伤后病理治疗方法至关重要。MicroRNAs (miRNAs, miRs) 是小的非编码 RNA,作为基因表达的转录后调节因子起作用。据报道,大鼠 TBI 后炎症相关的 microRNAs miR155 和 miR142 的表达增加。然而,这些 miRNA 在 TBI 后人脑中的表达尚未得到研究,它们的功能也不清楚。此外,循环 miR155 和 miR142 是候选生物标志物。所以,我们表征了 miR142 和 miR155 在遭受侧向液体冲击损伤的大鼠的病灶周围皮层和血浆中的表达,这是一种 TBI 模型,以及 TBI 后人类病灶周围皮层中的表达。我们在 TBI 后 2 周证明了大鼠病灶周围皮层中较高的 miR155 和 miR142 表达。在血浆中,miR155 与蛋白质相关,miR142 与细胞外囊泡相关,但它们的表达没有变化。在人类病灶周围皮层中,miR155 主要由活化的星形胶质细胞表达,而 miR142 主要由小胶质细胞、巨噬细胞和淋巴细胞表达。来自巨噬细胞样细胞的促炎介质刺激了星形胶质细胞中 miR155 的表达,而这些细胞中 miR142 的过表达进一步增强了活化星形胶质细胞的促炎状态。
更新日期:2020-05-27
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