Identification of key transcription factors associated with cerebral ischemia‑reperfusion injury based on gene‑set enrichment analysis

Zhang,Ying‑Ying; Wang,Kai; Liu,Yun‑E; Wang,Wei; Liu,Ao‑Fei; Zhou,Ji; Li,Chen; Zhang,Yi‑Qun; Zhang,Ai‑Ping; Lv,Jin; Jiang,Wei‑Jian

doi:10.3892/ijmm.2019.4159

Identification of key transcription factors associated with cerebral ischemia‑reperfusion injury based on gene‑set enrichment analysis

Authors:
- Ying‑Ying Zhang
- Kai Wang
- Yun‑E Liu
- Wei Wang
- Ao‑Fei Liu
- Ji Zhou
- Chen Li
- Yi‑Qun Zhang
- Ai‑Ping Zhang
- Jin Lv
- Wei‑Jian Jiang
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Affiliations: Department of Vascular Neurosurgery, New Era Stroke Care and Research Institute, The PLA Rocket Force Characteristic Medical Center, Beijing 100088, P.R. China, Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, P.R. China
Published online on: April 9, 2019 https://doi.org/10.3892/ijmm.2019.4159
Pages: 2429-2439
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cerebral ischemia‑reperfusion injury (CIRI) usually causes detrimental complications following reperfusion therapy in stroke patients. The present study systematically investigated the regulatory mechanism involved in the pathogenesis of CIRI using gene set enrichment analysis of the transient middle cerebral artery occlusion mouse stroke model. The results revealed a total of 13 CIRI‑related transcription factors (TFs), including CCAAT enhancer binding protein b (Cebpb), Cebpa, early growth response‑1, Fos, Rela, Jund, signal transduction and activator of transcription 5a/b, transformation related protein 53, GLI family zinc finger 2 (Gli2), Sp3, TF AP‑2 α (Tfap2a) and spleen focus forming virus proviral integration oncogene (Spi1). To the best of our knowledge, five TFs (Cebpa, Gli2, Sp3, Tfap2a and Spi1) were the first to be reported associated with CIRI in the present study. The five novel CIRI‑related TFs were mainly associated with pathways of inflammation and responses to reperfusion, including the tumor necrosis factor signaling pathway (Gli2, Spi1 and Tfap2a, P=0.0035, 0.0035 and 0.048, respectively), interleuking‑17 signaling pathway (Cebpa, Gli2, Sp3, Spi1 and Tfap2a, P=0.019, 0.047, 0.019, 0.035 and 0.005, respectively) and fluid shear stress and atherosclerosis (Gli2, Sp3, Spi1 and Tfap2a, P=0.047, 0.046, 0.013 and 0.003, respectively). These results may improve understanding of the potential molecular mechanism underlying the pathogenesis of CIRI at the genome‑wide level.

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