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MiR-1202 Exerts Neuroprotective Effects on OGD/R Induced Inflammation in HM Cell by Negatively Regulating Rab1a Involved in TLR4/NF-κB Signaling Pathway

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Abstract

Recent studies have shown that the level of miR-1202 in peripheral blood is closely related to brain activity and cognitive function in patients with depression, and it is involved in glioma pathological progress. However, the correlation between miR-1202 and neuroinflammation has not been reported. The expressions of miR-1202 and small GTP-ase Rab1a at mRNA level were detected in oxygen-glucose deprivation (OGD)/reoxygenation (R) induced human microglial cells (HM cells) by RT-qPCR at different time points within 48 h. Dual luciferase report assay and immunofluorescence staining were performed to confirm whether Rab1a was the potential target of miR-1202. The toll-like receptor 4 (TLR4)/nuclear factor kappa beta (NF-κB) signal related proteins (TLR4, P65, p-P65, IκBa) and the downstream pro-inflammation factors pro-IL-1β, pro-IL-18, as well as the inflammation factors interleukin-1β (IL-1β) and interleukin-18 (IL-18) were detected by western-blotting. The expression level of TLR4 on cell surface was detected by flow cytometry. Down-regulation of miR-1202 and up-regulation of Rab1a were found in OGD/R induced HM cells. In addition, miR-1202 was identified to directly target Rab1a and down-regulate its expression. Moreover, over-expression of miR-1202 suppressed the activation of TLR4/NF-κB inflammatory signaling pathway. Rab1a can increase the expression level of TLR4 on the surface of OGD/R induced HM cells. MiR-1202 exerts neuroprotective effect by negatively regulating its target protein Rab1a, which can inactivate TLR4/NF-κB-involved inflammatory signaling pathway in OGD/R induced HM cells. These findings provide potential therapeutic targets for ischemic stroke.

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Author notes

  1. Shuhuan Song and Yan Pan are co-first authors and have contributed equally to the work.

Authors and Affiliations

  1. Department of Neurology Second District, Chengwu People’s Hospital, No. 66, Bole Street, Heze, 274200, Shandong, China

    Shuhuan Song

  2. Department of Neurology, Gaomi People’s Hospital, No. 77, government street, Gaomi, 261500, Shandong, China

    Yan Pan

  3. Department of Neurology, Anqiu People’s Hospital, No. 246, Jiankang Road, Anqiu, 262100, Shandong, China

    Hua Li

  4. Department of Cardiothoracic Surgery, Zhangqiu District People’s Hospital, Jinan, 250200, Shandong, China

    Honghua Zhen

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  1. Shuhuan Song
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  2. Yan Pan
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  3. Hua Li
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  4. Honghua Zhen
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Correspondence to Yan Pan.

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Song, S., Pan, Y., Li, H. et al. MiR-1202 Exerts Neuroprotective Effects on OGD/R Induced Inflammation in HM Cell by Negatively Regulating Rab1a Involved in TLR4/NF-κB Signaling Pathway. Neurochem Res 45, 1120–1129 (2020). https://doi.org/10.1007/s11064-020-02991-7

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  • DOI: https://doi.org/10.1007/s11064-020-02991-7

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