Regulation of serum response factor by miRNA-200 and miRNA-9 modulates oligodendrocyte progenitor cell differentiation.

Regulation of serum response factor by miRNA-200 and miRNA-9 modulates oligodendrocyte progenitor cell differentiation.
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DOI:
10.1002/glia.22406
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发表时间:
2012-12
期刊:
影响因子:
6.2
通讯作者:
Zhang, Zheng Gang
Zhang, Zheng Gang
中科院分区:
医学1区
文献类型:
--
作者:
Buller, Benjamin;Chopp, Michael;Ueno, Yuji;Zhang, Li;Zhang, Rui Lan;Morris, Daniel;Zhang, Yi;Zhang, Zheng Gang

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血清反应因子(SRF)是反式激活基因的转录因子,迄今为止,已经在少突胶质细胞(OL)分化中暗示,它尚未在脑缺血中研究。 SRF在体外的少突胶质细胞分化。和脑缺血性白质区域中的miR-200家族,CCG-1423(一种特定的SRF功能抑制剂)抑制SRF的抑制作用,使OPC无法区分OLS。 200在培养的OPC中,抑制了SRF的表达并抑制OPC分化,MiR-9的共表达和miR-200为了证明中风上调OPC和OLS中的SRF表达,并且SRF水平由miRNA介导并调节OPC分化。
Serum response factor (SRF) is a transcription factor that transactivates actin associated genes, and has been implicated in oligodendrocyte (OL) differentiation. To date, it has not been investigated in cerebral ischemia. We investigated the dynamics of SRF expression after stroke in vivo and the role of SRF in oligodendrocyte differentiation in vitro. Using immunohistochemistry, we found that SRF was upregulated in OLs and OL precursor cells (OPCs) after stroke. Moreover, upregulation of SRF was concurrent with downregulation of the microRNAs (miRNAs) miR-9 and the miR-200 family in the ischemic white matter region, the corpus callosum. Inhibition of SRF activation by CCG-1423, a specific inhibitor of SRF function, blocked OPCs from differentiating into OLs. Over-expression of miR-9 and miR-200 in cultured OPCs suppressed SRF expression and inhibited OPC differentiation. Moreover, co-expression of miR-9 and miR-200 attenuated activity of a luciferase reporter assay containing the Srf 3′ untranslated region (UTR). Collectively, this study is the first to show that stroke upregulates SRF expression in OPCs and OLs, and that SRF levels are mediated by miRNAs and regulate OPC differentiation.
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