The synthetic NCAM-derived peptide, FGL, modulates the transcriptional response to traumatic brain injury
The synthetic NCAM-derived peptide, FGL, modulates the transcriptional response to traumatic brain injury
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合成的 NCAM 衍生肽 FGL 调节对创伤性脑损伤的转录反应
DOI：
10.1016/j.neulet.2008.03.070
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发表时间：
2008
影响因子：
2.5
通讯作者：
M. Penkowa
中科院分区：
文献类型：
--
作者：
M. V. Pedersen;R. B. Helweg;F. Nielsen;V. Berezin;E. Bock;M. Penkowa
大脑对创伤性脑损伤（TBI）的反应包括大量参与内源性炎症反应和损伤后防御机制的蛋白质的上调和下调。本研究采用微阵列分析的方法分析了低温诱导的TBI的全局基因表达谱。青少年大鼠接受创伤性脑损伤，并接受安慰剂或神经细胞粘附分子（NCAM）衍生的成纤维细胞生长因子受体（FGFR）激动剂FGL肽治疗，FGL肽已被证明具有神经保护作用。在病变后不同时间点（6h、1天和4天）测量mRNA水平。观察损伤、治疗和损伤-治疗相互作用的影响。仅TBI就会导致大量基因受到影响。对损伤和治疗相互作用的分析表明，与损伤和安慰剂治疗相比，损伤和fgl治疗之间的相互作用有明显的效果。单独受创伤性脑损伤影响的基因包括炎症标志物、蛋白激酶、离子通道成员和生长因子。fgl与TBI的相互作用改变了细胞凋亡、信号转导和代谢调控基因。在未受伤的动物中，fgl使调节信号传导、运输和细胞骨架维持的基因显著增加。因此，我们的研究结果支持了FGL具有神经保护作用的假设。
Cerebral responses to traumatic brain injury (TBI) include up- and downregulation of a vast number of proteins involved in endogenous inflammatory responses and defense mechanisms developing postinjury. The present study analyzed the global gene expression profile in response to cryo-induced TBI by means of microarray analysis. Adolescent rats were subjected to TBI and treated with either placebo or a neural cell adhesion molecule (NCAM)-derived fibroblast growth factor receptor (FGFR) agonist, FGL peptide, which has been demonstrated to have neuroprotective effects. mRNA levels were measured at various time-points postlesion (6h, 1 day and 4 days). The effects of injury, treatment, and injury-treatment interaction were observed. TBI alone rendered a large number of genes affected. Analysis of lesion and treatment interactions resulted in a clear effect of the interaction between injury and FGL-treatment compared to injury and placebo-treatment. Genes affected by TBI alone included inflammation markers, protein kinases, ion channel members and growth factors. Genes encoding regulators of apoptosis, signal transduction and metabolism were altered by the interaction between FGL-treatment and TBI. FGL-treatment in non-injured animals rendered genes regulating signaling, transport and cytoskeleton maintenance significantly increased. Thus, the hypothesis of a putative neuroprotective role of FGL was supported by our findings.