Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Glia. 2012 Dec;60(12):1906-14. doi: 10.1002/glia.22406. Epub 2012 Aug 20.
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 OL 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 micro-RNAs (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. Overexpression 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. 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.
血清反应因子（SRF）是一种转录因子，可激活肌动蛋白相关基因，并与少突胶质细胞（OL）分化有关。迄今为止，它在脑缺血中尚未被研究过。我们研究了体内卒中后 SRF 表达的动态变化，以及 SRF 在 OL 分化中的作用。通过免疫组织化学，我们发现卒中后 OL 和 OL 前体细胞（OPC）中的 SRF 上调。此外，SRF 的上调与缺血性白质区域（胼胝体）中 micro-RNAs（miRNAs）miR-9 和 miR-200 家族的下调同时发生。特异性抑制 SRF 功能的 CCG-1423 抑制 SRF 激活，阻止 OPC 分化为 OL。在培养的 OPC 中过表达 miR-9 和 miR-200 抑制 SRF 表达并抑制 OPC 分化。此外，miR-9 和 miR-200 的共表达减弱了包含 Srf 3'非翻译区的荧光素酶报告基因检测的活性。总的来说，这项研究首次表明卒中上调了 OPC 和 OL 中 SRF 的表达，并且 SRF 水平受 miRNA 调控并调节 OPC 分化。
