Time-dependent variation of pathways and networks in a 24-hour window after cerebral ischemia-reperfusion injury

BMC Systems Biology

Yong-Yan Wang³  Zhong Wang³  Yi-Jun Zhao¹  Shan-Shan Guo²  Hai-Xia Li⁴  Ya-Nan Yu³  Zhi-Wei Jing¹  Ying-Ying Zhang³  Bing Li⁵  Yuan Li⁶  Jun Liu³  Li-Ying Wang³ 

[1] China Academy of Chinese Medical Sciences, Dongzhimennei Nanxiaojie 16#, Beijing 100700, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongzhimennei Nanxiaojie 16#, Beijing 100700, China;Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei Nanxiaojie 16#, Beijing 100700, China;Guang’anmen Hospital, China Academy of China Medical Sciences, No.5 Beixiange, Beijing 100053, China;Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Dongzhimennei Nanxiaojie 16#, Beijing 100700, China;Beijing University of Chinese Medicine, No. 11 East Road, North of 3rd Ring Road, Beijing 100029, China

关键词: Process network;    Pathway;    Dynamic variation;    Ischemia-reperfusion injury;   

Others  :  1159566
DOI  :  10.1186/s12918-015-0152-4

 received in 2014-06-14, accepted in 2015-02-17,  发布年份 2015

【 摘 要 】

Background

Cerebral ischemia-reperfusion injury may simultaneously result in functional variation of multiple genes/pathways. However, most prior time-sequence studies on its pathomechanism only focused on a single gene or pathway. Our study aimed to systematically analyze the time-dependent variation in the expression of multiple pathways and networks within 24 h after cerebral ischemia-reperfusion injury.

Results

By uploading 374 ischemia-related genes into the MetaCore software, the variation in the expression of multiple pathways and networks in 3 h, 12 h, and 24 h after cerebral ischemia-reperfusion injury had been analyzed. The conserved TNFR1-signaling pathway, among the top 10 pathways, was consistently enriched in 3 h, 12 h, and 24 h groups. Three overlapping pathways were found between 3 h and 12 h groups; 2 between 12 h and 24 h groups; and 1 between 3 h and 24 h groups. Five, 4, and 6 non-overlapping pathways were observed in 3 h, 12 h, and 24 h groups, respectively. Apart from pathways reported by earlier studies, we identified a novel pathway related to the time-dependent development of cerebral ischemia pathogenesis. The process of apoptosis stimulation by external signals, among the top 10 processes, was consistently enriched in 3 h, 12 h, and 24 h groups; 2, 1, and 2 processes overlapped between 3 h and 12 h groups, 12 h and 24 h groups, and 3 h and 24 h groups, respectively. Four, 5, and 5 non-overlapping processes were found in 3 h, 12 h and 24 h groups, respectively. The presence of apoptotic processes was observed in all the 3 groups; while anti-apoptotic processes only existed in 3 h and 12 h groups. Additionally, according to node degree, network comparison identified 1, 8,and 5 important genes or proteins (e.g. Pyk2, PKC, E2F1, and VEGF-A) in 3 h, 12 h, and 24 h groups, respectively. The Jaccard similarity index revealed a higher level of similarity between 12 h and 24 h groups than that between 3 h and 12 h groups.

Conclusion

Time-dependent treatment can be utilized to reduce apoptosis, which may activate anti-apoptotic pathways within 12 h after cerebral ischemia-reperfusion injury. Pathway and network analyses may help identify novel pathways and genes implicated in disease pathogenesis.

【 授权许可】

   
2015 Wang et al.; licensee BioMed Central.

【 图 表 】

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