Hypoxia-induced miR-17-5p ameliorates the viability reduction of astrocytes via targeting p21

J.-F. Li, P.-M. Wang, N.-N. Zhang, X. Zhang, J. Guan, Z. Ye, J.-Y. Yan

Department of Rehabilitation, the Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China. jinyu1973yan@163.com

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• Neurology

OBJECTIVE: Glial scars are widely seen as a mechanical barrier to central nervous system regeneration. Up to now, several studies have addressed and clarified how different lesion microenvironment properties affect astrogliosis. In particular, hypoxia induces the astrocyte astrogliosis, and thus promotes the formation of glial scars. However, little is known about the mechanism underlining such process. In the present study, we investigated the regulation by the miR-17-5p on the hypoxia-induced viability via targeting p21.

MATERIALS AND METHODS: We examined the expression of miR-15a, miR-16, miR-17-5p, hypoxia inducible factor-1α (HIF-1α) and p21 in the astrocytes under hypoxia, with quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) methods. Then investigated the regulatory role of miR-17-5p on the level of HIF-1α and p21, with qRT-PCR, WB and luciferase reporting assay, and examined the activity of astrocytes under normoxia or hypoxia.

RESULTS: Results demonstrated that miR-15a, miR-16, miR-17-5p were significantly upregulated, while HIF-1α and p21 were markedly downregulated in the hypoxia-treated astrocytes. And the transfection with miR-17-5p mimics significantly downregulated the expression of HIF-1α and p21 in such cells. And the luciferase reporter assay confirmed the targeting inhibiting of p21 by miR-17-5p in astrocytes. Moreover, the viability of astrocytes was significantly upregulated by the miR-17-5p mimics transfection under the hypoxia condition.

CONCLUSIONS: Our novel data suggest that the upregulated miR-17-5p contributes to the proliferation of astrocytes, in response to hypoxia, implying the potential role of miR-17-5p in the formation of glial scars.

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