Vascular Endothelial Growth Factor and Erythropoietin Show Different Expression Patterns in the Early and Late Hypoxia Preconditioning Phases and May Correlate with DNA Methylation Status in the Mouse Hippocampus
机构：[1]Department of Laboratory Medicine, Center for Translational Medicine, the Third People’s Hospital of Longgang District, Shenzhen, China.深圳市康宁医院深圳医学信息中心[2]Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College of Neuroscience Institute, Baotou Medical College, Inner Mongolia, China.内蒙古科技大学包头医学院[3]Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.科技平台低氧适应转化医学北京市重点实验室首都医科大学宣武医院[4]Department of Neurology, The Second Affiliated Hospital of Shandong First Medical University, Shandong, China.[5]Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California, USA.[6]Department of Neurosurgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia, China.内蒙古科技大学包头医学院[7]Joint Laboratory of South China Hospital Affiliated to Shenzhen University and Third People’s Hospital of Longgang District, Shenzhen University, Shenzhen, China.
Liu, Na, Yanbo Zhang, Pu Zhang, Kerui Gong, Chunyang Zhang, Kai Sun, and Guo Shao. Vascular endothelial growth factor and erythropoietin show different expression patterns in the early and late hypoxia preconditioning phases and may correlate with DNA methylation status in the mouse hippocampus. High Alt Med Biol. 00:000-000, 2022.Background: Vascular endothelial growth factor (VEGF) and erythropoietin (EPO) have been proven to participate in neuroprotection induced by hypoxia preconditioning (HPC), and they can be regulated by hypoxia-inducible factor 1 (HIF-1). It has been reported that DNA methylation can affect VEGF and EPO expression. This study aimed to explore the expression of VEGF and EPO in the early phase and late phase of HPC and whether their expression was affected by DNA methylation.Method: Acute repeated HPC mice were used as the animal model, and detection of molecular changes was performed immediately (early phase) and 1 day (late phase) after HPC treatment. The mRNA and protein expression levels of VEGF, EPO, and DNA methyltransferases (DNMTs) in the hippocampi were measured by real-time polymerase chain reaction and western blotting, respectively. The activity of DNMTs and global methylation levels were analyzed by enzyme-linked immunosorbent assay. DNA methylation levels of VEGF and EPO promoters, which were catalyzed by DNMTs, were determined by bisulfite-modified DNA sequencing.Results: The expression of VEGF was increased in the early phase and late phase of HPC (p < 0.05), whereas the expression of EPO was unchanged in the early phase (p > 0.05) of HPC and was increased in the late phase (p < 0.05). VEGF and EPO expression were negatively correlated with the DNA methylation levels of their promoters. DNMT3A and DNMT3B were decreased in the early phase and late phase (p < 0.05), whereas DNMT1 was unchanged in the early phase and late phase (p > 0.05).Conclusions: Our data demonstrated that DNMTs affect VEGF and EPO expression by regulating the DNA methylation levels of the promoters of VEGF and EPO.
基金：
National Natural Science Foundation of China [81660307, 82060337]; Funds for the Cultivation of Aca-demic Leaders in The Second Affiliated Hospital of Shan-dong First Medical University; Shenzhen Longgang DistrictEconomic and Technological Development Special Fund Medical, Health Technology Plan Project [LGKCYLWS2021000033]; Shenzhen Science and Technology PlanProject [JCYJ20220531092412028]
第一作者机构：[1]Department of Laboratory Medicine, Center for Translational Medicine, the Third People’s Hospital of Longgang District, Shenzhen, China.[2]Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College of Neuroscience Institute, Baotou Medical College, Inner Mongolia, China.[3]Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.
通讯作者：
通讯机构：[1]Department of Laboratory Medicine, Center for Translational Medicine, the Third People’s Hospital of Longgang District, Shenzhen, China.[2]Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College of Neuroscience Institute, Baotou Medical College, Inner Mongolia, China.[3]Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.[6]Department of Neurosurgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia, China.[7]Joint Laboratory of South China Hospital Affiliated to Shenzhen University and Third People’s Hospital of Longgang District, Shenzhen University, Shenzhen, China.[*1]Department of Neurosurgery The First Affiliated Hospital of Baotou Medical College Inner Mongolia 014010 China[*2]Department of Laboratory Medicine Center for Translational Medicine the Third People’s Hospital of Longgang District Shenzhen 518112 China
推荐引用方式(GB/T 7714)：
Liu Na,Zhang Yanbo,Zhang Pu,et al.Vascular Endothelial Growth Factor and Erythropoietin Show Different Expression Patterns in the Early and Late Hypoxia Preconditioning Phases and May Correlate with DNA Methylation Status in the Mouse Hippocampus[J].HIGH ALTITUDE MEDICINE & BIOLOGY.2022,23(4):361-368.doi:10.1089/ham.2021.0108.
APA：
Liu, Na,Zhang, Yanbo,Zhang, Pu,Gong, Kerui,Zhang, Chunyang...&Shao, Guo.(2022).Vascular Endothelial Growth Factor and Erythropoietin Show Different Expression Patterns in the Early and Late Hypoxia Preconditioning Phases and May Correlate with DNA Methylation Status in the Mouse Hippocampus.HIGH ALTITUDE MEDICINE & BIOLOGY,23,(4)
MLA：
Liu, Na,et al."Vascular Endothelial Growth Factor and Erythropoietin Show Different Expression Patterns in the Early and Late Hypoxia Preconditioning Phases and May Correlate with DNA Methylation Status in the Mouse Hippocampus".HIGH ALTITUDE MEDICINE & BIOLOGY 23..4(2022):361-368
