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新生大鼠缺氧缺血性脑损伤中差异表达基因的生物信息学分析

[Bioinformatic Analysis of Differentially Expressed Genes Involved in the Post-hypoxic Ischemic Brain Damage of Newborn Rats].

作者信息

Shi Jing, Tang Jun, Mu De-Zhi

机构信息

Department of Pediatrics, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education,Chengdu 610041,China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2016 Sep;47(5):722-726.

PMID:28598087
Abstract

OBJECTIVES

To analyze the differentially expressed genes (DEGs) in cerebral cortices of rats which were seven weeks after neonatal hypoxic ischemic brain damage (HIBD) and elucidate the biological significance of the DEGs.

METHODS

The gene expression profile of GSE37777, including 4 HI samples subjected to HIBD and 4 normal controls, was downloaded from the Gene Expression Omnibus database (GEO). DEGs were screened using the R package in HIBD groups compared with normal controls. Pathway enrichment analysis was carried out using the Cytoscape plug-in ClueGO+Cluepedia and a functionally grouped pathway network of DEGs was constructed and analyzed. Besides, the protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape.

RESULTS

A total of 973 DEGs were identified in HIBD group compared with the control group, including 599 up-regulated and 374 down-regulated genes. Furthermore, a functionally grouped pathway network of DEGs was constructed and hedgehog signaling pathway were identified. and which were Hedgehog signaling pathway-related genes and the Wnt signaling pathway-related genes and were up-regulated in HIBD group. Furthermore, Ccnd1, Shh, Ret and Gli3 were hub proteins in the PPI network and up-regulated Shh and Dhh, down-regulated Ccnd1 and Gli3 were noticed.

CONCLUSIONS

Our results showed that Hedgehog and Wnt signaling pathway may be activated HIBD group. Additionally, Shh and Ret which were related to the repair process of brain damage were up-regulated. Continuous repair process may exist in the cerebral cortices of rats which were seven weeks after neonatal HIBD.

摘要

目的

分析新生大鼠缺氧缺血性脑损伤(HIBD)7周后大脑皮质中的差异表达基因(DEGs),并阐明这些DEGs的生物学意义。

方法

从基因表达综合数据库(GEO)下载GSE37777的基因表达谱,包括4个HIBD的HI样本和4个正常对照。与正常对照相比,使用R包在HIBD组中筛选DEGs。使用Cytoscape插件ClueGO+Cluepedia进行通路富集分析,并构建和分析DEGs的功能分组通路网络。此外,使用检索相互作用基因的搜索工具(STRING)数据库构建蛋白质-蛋白质相互作用(PPI)网络,并使用Cytoscape进行可视化。

结果

与对照组相比,HIBD组共鉴定出973个DEGs,包括599个上调基因和374个下调基因。此外,构建了DEGs的功能分组通路网络,并鉴定出刺猬信号通路。刺猬信号通路相关基因和Wnt信号通路相关基因在HIBD组中上调。此外,Ccnd1、Shh、Ret和Gli3是PPI网络中的枢纽蛋白,注意到Shh和Dhh上调,Ccnd1和Gli3下调。

结论

我们的结果表明,刺猬和Wnt信号通路可能在HIBD组中被激活。此外,与脑损伤修复过程相关的Shh和Ret上调。新生HIBD 7周后的大鼠大脑皮质可能存在持续的修复过程。

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