Wong Yung-Hao, Wu Chia-Chou, Lai Hsien-Yong, Jheng Bo-Ren, Weng Hsing-Yu, Chang Tzu-Hao, Chen Bor-Sen
BMC Syst Biol. 2015;9 Suppl 6(Suppl 6):S4. doi: 10.1186/1752-0509-9-S6-S4. Epub 2015 Dec 9.
Molecular signaling of angiogenesis begins within hours after initiation of a stroke and the following regulation of endothelial integrity mediated by growth factor receptors and vascular growth factors. Recent studies further provided insights into the coordinated patterns of post-stroke gene expressions and the relationships between neurodegenerative diseases and neural function recovery processes after a stroke.
Differential protein-protein interaction networks (PPINs) were constructed at 3 post-stroke time points, and proteins with a significant stroke relevance value (SRV) were discovered. Genes, including UBC, CUL3, APP, NEDD8, JUP, and SIRT7, showed high associations with time after a stroke, and Ingenuity Pathway Analysis results showed that these post-stroke time series-associated genes were related to molecular and cellular functions of cell death, cell survival, the cell cycle, cellular development, cellular movement, and cell-to-cell signaling and interactions. These biomarkers may be helpful for the early detection, diagnosis, and prognosis of ischemic stroke.
This is our first attempt to use our theory of a systems biology framework on strokes. We focused on 3 key post-stroke time points. We identified the network and corresponding network biomarkers for the 3 time points, further studies are needed to experimentally confirm the findings and compare them with the causes of ischemic stroke. Our findings showed that stroke-associated biomarker genes at different time points were significantly involved in cell cycle processing, including G2-M, G1-S and meiosis, which contributes to the current understanding of the etiology of stroke. We hope this work helps scientists reveal more hidden cellular mechanisms of stroke etiology and repair processes.
血管生成的分子信号在中风开始后的数小时内启动，随后由生长因子受体和血管生长因子介导对内皮完整性进行调节。最近的研究进一步深入了解了中风后基因表达的协调模式以及神经退行性疾病与中风后神经功能恢复过程之间的关系。
在中风后的3个时间点构建了差异蛋白质-蛋白质相互作用网络（PPINs），并发现了具有显著中风相关性值（SRV）的蛋白质。包括UBC、CUL3、APP、NEDD8、JUP和SIRT7在内的基因与中风后的时间高度相关， Ingenuity通路分析结果表明，这些中风后时间序列相关基因与细胞死亡、细胞存活、细胞周期、细胞发育、细胞运动以及细胞间信号传导和相互作用的分子和细胞功能有关。这些生物标志物可能有助于缺血性中风的早期检测、诊断和预后评估。
这是我们首次尝试将系统生物学框架理论应用于中风研究。我们聚焦于中风后的3个关键时间点。我们确定了这3个时间点的网络及相应的网络生物标志物，需要进一步的研究通过实验来证实这些发现，并将其与缺血性中风的病因进行比较。我们的研究结果表明，不同时间点的中风相关生物标志物基因显著参与细胞周期进程，包括G2-M期、G1-S期和减数分裂，这有助于当前对中风病因的理解。我们希望这项工作能帮助科学家揭示更多中风病因和修复过程中隐藏的细胞机制。
