Temporal Gene Expression Profiles after Focal Cerebral Ischemia in Mice.
Temporal Gene Expression Profiles after Focal Cerebral Ischemia in Mice.
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小鼠局灶性脑缺血后的时间基因表达谱
DOI：
10.14336/ad.2017.0424
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发表时间：
2018-04
影响因子：
7.4
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Zhang C;Zhu Y;Wang S;Zachory Wei Z;Jiang MQ;Zhang Y;Pan Y;Tao S;Li J;Wei L
缺血性卒中后病变区域会触发一系列的病理过程。不幸的是，我们对这些复杂的分子事件的理解是不完整的。在这项研究中，我们试图更好地了解缺血性卒中后发生的详细的分子和炎症事件。采用RNA-seq技术鉴定小鼠局灶性脑缺血后d1、d3、d7、d14、d21的全基因表达谱。然后分析了基于基因本体论(GO)和京都基因与基因组百科全书(KEGG)术语的差异表达基因(DIG)的浓缩分析。选择卒中后显著表达的炎症相关基因进行分析，并报道了促炎和抗炎基因的时间表达模式。这些数据表明，脑缺血后DEG数量呈累积性增加。总体而言，D11967°，D3 2280°，D7 2631°，D14 5516°，D21 7093°。显着丰富的围棋术语也增加了。58条围棋术语和18条KEGG通路在所有检查时间点均显著丰富。我们确定了87个DEG，它们在功能上与炎症反应有关。致炎相关基因CD16、CD32、CD86、CD11b、肿瘤坏死因子α(肿瘤坏死因子α)、白介素1β(IL-1β)的表达水平随时间延长而升高，并于第14天达到高峰。抗炎相关基因精氨酸酶1(Arg1)和几丁质酶样3(YM1)在脑缺血后d1达高峰，而IL-10、转化生长因子β(转化生长因子β)和CD206在脑缺血后1 d达高峰，7~14 d达高峰。这些基因谱变化可能与小胶质细胞/巨噬细胞表型变化有关，并可能在星形胶质细胞激活中发挥作用。这项研究为实验性缺血性卒中后发生的分子事件和病理机制提供了新的见解和详细的信息。
A cascade of pathological processes is triggered in the lesion area after ischemic stroke. Unfortunately, our understanding of these complicated molecular events is incomplete. In this investigation, we sought to better understand the detailed molecular and inflammatory events occurring after ischemic stroke. RNA-seq technology was used to identify whole gene expression profiles at days (D1, D3, D7, D14, D21) after focal cerebral ischemia in mice. Enrichment analyses based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for the differentially expressed genes (DEGs) were then analyzed. Inflammation-related genes that were significantly expressed after stroke were selected for analysis and the temporal expression patterns of pro-inflammatory and anti-inflammatory genes were reported. These data illustrated that the number of DEGs increased accumulatively after cerebral ischemia. In summary, there were 1967 DEGs at D1, 2280 DEGs at D3, 2631 DEGs at D7, 5516 DEGs at D14 and 7093 DEGs at D21. The significantly enriched GO terms also increased. 58 GO terms and 18 KEGG pathways were significantly enriched at all inspected time points. We identified 87 DEGs which were functionally related to inflammatory responses. The expression levels of pro-inflammation related genes CD16, CD32, CD86, CD11b, Tumour necrosis factor α (TNF-α), Interleukin 1β (IL-1β) increased over time and peaked at D14. Anti-inflammation related genes Arginase 1 (Arg1) and Chitinase-like 3 (Ym1) peaked at D1 while IL-10, Transforming growth factor β (TGF-β) and CD206, which were induced at 1 day after cerebral ischemia, peaked by 7 to 14 days. These gene profile changes were potentially linked to microglia/macrophage phenotype changes and could play a role in astroglial activation. This study supplies new insights and detailed information on the molecular events and pathological mechanisms that occur after experimental ischemic stroke.