Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury
Abstract Background This study aimed to explore the molecular mechanism of estrogen-mediated neuroprotection in the relief of cerebral ischemic injury. The gene expression profiles were downloaded from Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified using...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | BMC Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12863-018-0630-y |
| _version_ | 1811291954139365376 |
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| author | Jiaxuan He Ya Gao Gang Wu Xiaoming Lei Yong Zhang Weikang Pan Hui Yu |
| author_facet | Jiaxuan He Ya Gao Gang Wu Xiaoming Lei Yong Zhang Weikang Pan Hui Yu |
| author_sort | Jiaxuan He |
| collection | DOAJ |
| description | Abstract Background This study aimed to explore the molecular mechanism of estrogen-mediated neuroprotection in the relief of cerebral ischemic injury. The gene expression profiles were downloaded from Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified using limma package in R software. Further, DEGs were subjected to Gene Ontology (GO) cluster analysis using online Gene Ontology Enrichment Analysis Software Toolkit and to GO functional enrichment analysis using DAVID software. Using the Gene Set Analysis Toolkit V2, enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways was performed. In addition, protein-protein interaction (PPI) network was constructed using STRING database, and submodule analysis of PPI network. Lastly, the significant potential target sites of microRNAs (miRNAs) were predicted using Molecular Signatures Database, and the function analysis of targets of predicted miRNA was also performed using DAVID software. Results In total, 321 DEGs were screened in the estrogen-treated sample. The DEGs were mainly associated with intracellular signaling and metabolic pathways, such as calcium channel, calcineurin complex, insulin secretion, low-density lipoprotein reconstruction, and starch or sugar metabolism. In addition, GO enrichment analysis indicated an altered expression of the genes related to starch and sucrose metabolism, retinol metabolism, anti-apoptosis (eg., BDNF and ADAM17) and response to endogenous stimulus. The constructed PPI network comprised of 243 nodes and 590 interaction pairs, and four submodules were obtained from PPI network. Among the module d, four glutamate receptors as Gria4, Gria3, Grin3a and Grik4 were highlighted. Further, 5 novel potential regulatory miRNAs were also predicted. MIR-338 and MIR520D were closely associated with cell cycle, while the targets of MIR-376A and MIR-376B were only involved in cell soma. Conclusions The DEGs in estrogen-treated samples are closely associated with calcium channel, glutamate induced excitotoxicity and anti-apoptotic activity. In addition, some functionally significant DEGs such as BDNF, ADAM17, Gria4, Gria3, Grin3a, Grik4, Gys2 and Ugtla2, and new miRNAs like MIR-338 and MIR-376A were identified, which may serve as potential therapeutic targets for the effective treatment of cerebral ischemic injury. |
| first_indexed | 2024-04-13T04:38:03Z |
| format | Article |
| id | doaj.art-9d0a100d57e1456ab3e6a77d12c32240 |
| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-04-13T04:38:03Z |
| publishDate | 2018-07-01 |
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| series | BMC Genetics |
| spelling | doaj.art-9d0a100d57e1456ab3e6a77d12c322402022-12-22T03:02:07ZengBMCBMC Genetics1471-21562018-07-0119111010.1186/s12863-018-0630-yMolecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injuryJiaxuan He0Ya Gao1Gang Wu2Xiaoming Lei3Yong Zhang4Weikang Pan5Hui Yu6Department of Anesthesia, Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Pediatric surgery, Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Anesthesia, Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Anesthesia, Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Anesthesia, Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Pediatric surgery, Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Pediatric surgery, Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background This study aimed to explore the molecular mechanism of estrogen-mediated neuroprotection in the relief of cerebral ischemic injury. The gene expression profiles were downloaded from Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified using limma package in R software. Further, DEGs were subjected to Gene Ontology (GO) cluster analysis using online Gene Ontology Enrichment Analysis Software Toolkit and to GO functional enrichment analysis using DAVID software. Using the Gene Set Analysis Toolkit V2, enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways was performed. In addition, protein-protein interaction (PPI) network was constructed using STRING database, and submodule analysis of PPI network. Lastly, the significant potential target sites of microRNAs (miRNAs) were predicted using Molecular Signatures Database, and the function analysis of targets of predicted miRNA was also performed using DAVID software. Results In total, 321 DEGs were screened in the estrogen-treated sample. The DEGs were mainly associated with intracellular signaling and metabolic pathways, such as calcium channel, calcineurin complex, insulin secretion, low-density lipoprotein reconstruction, and starch or sugar metabolism. In addition, GO enrichment analysis indicated an altered expression of the genes related to starch and sucrose metabolism, retinol metabolism, anti-apoptosis (eg., BDNF and ADAM17) and response to endogenous stimulus. The constructed PPI network comprised of 243 nodes and 590 interaction pairs, and four submodules were obtained from PPI network. Among the module d, four glutamate receptors as Gria4, Gria3, Grin3a and Grik4 were highlighted. Further, 5 novel potential regulatory miRNAs were also predicted. MIR-338 and MIR520D were closely associated with cell cycle, while the targets of MIR-376A and MIR-376B were only involved in cell soma. Conclusions The DEGs in estrogen-treated samples are closely associated with calcium channel, glutamate induced excitotoxicity and anti-apoptotic activity. In addition, some functionally significant DEGs such as BDNF, ADAM17, Gria4, Gria3, Grin3a, Grik4, Gys2 and Ugtla2, and new miRNAs like MIR-338 and MIR-376A were identified, which may serve as potential therapeutic targets for the effective treatment of cerebral ischemic injury.http://link.springer.com/article/10.1186/s12863-018-0630-yBrain ischemic injuryEstrogenDifferentially expressed genesmicroRNAsPathway enrichment analysis |
| spellingShingle | Jiaxuan He Ya Gao Gang Wu Xiaoming Lei Yong Zhang Weikang Pan Hui Yu Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury BMC Genetics Brain ischemic injury Estrogen Differentially expressed genes microRNAs Pathway enrichment analysis |
| title | Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury |
| title_full | Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury |
| title_fullStr | Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury |
| title_full_unstemmed | Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury |
| title_short | Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury |
| title_sort | molecular mechanism of estrogen mediated neuroprotection in the relief of brain ischemic injury |
| topic | Brain ischemic injury Estrogen Differentially expressed genes microRNAs Pathway enrichment analysis |
| url | http://link.springer.com/article/10.1186/s12863-018-0630-y |
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