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Critical Reviews™ in Eukaryotic Gene Expression

Publicou 6 edições por ano

ISSN Imprimir: 1045-4403

ISSN On-line: 2162-6502

The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) IF: 1.6 To calculate the five year Impact Factor, citations are counted in 2017 to the previous five years and divided by the source items published in the previous five years. 2017 Journal Citation Reports (Clarivate Analytics, 2018) 5-Year IF: 2.2 The Immediacy Index is the average number of times an article is cited in the year it is published. The journal Immediacy Index indicates how quickly articles in a journal are cited. Immediacy Index: 0.3 The Eigenfactor score, developed by Jevin West and Carl Bergstrom at the University of Washington, is a rating of the total importance of a scientific journal. Journals are rated according to the number of incoming citations, with citations from highly ranked journals weighted to make a larger contribution to the eigenfactor than those from poorly ranked journals. Eigenfactor: 0.00058 The Journal Citation Indicator (JCI) is a single measurement of the field-normalized citation impact of journals in the Web of Science Core Collection across disciplines. The key words here are that the metric is normalized and cross-disciplinary. JCI: 0.33 SJR: 0.345 SNIP: 0.46 CiteScore™:: 2.5 H-Index: 67

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The Molecular Mechanism of EPO Regulates the Angiogenesis after Cerebral Ischemia through AMPK-KLF2 Signaling Pathway

Volume 29, Edição 2, 2019, pp. 105-112
DOI: 10.1615/CritRevEukaryotGeneExpr.2019029018
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RESUMO

Objective: In this study, the molecular mechanism by which EPO regulates the angiogenesis after cerebral ischemia through AMPK-KLF2 signaling pathway was investigated. Methods: Sixty healthy, male, C57BL/6 mice were randomly divided into three groups of 20 mice: a sham group, the middle cerebral artery occlusion (MCAO) group, and a MCAO+EPO treatment group. The MCAO model was established using a modified ZeaLonga method. Mice in the EPO treatment group were injected with EPO immediately after reperfusion (5000 IU/kg), and EPO was injected the following day. The number of mouse deaths and neurologic function scores were recorded during the experiment. On day 7 after cerebral ischemia, brain tissue proteins were extracted. The following proteins expressions were detected by western blot assay: EPO, vascular endothelial growth factor (VEGE), vascular endothelial growth factor receptor (KDR), adenosine activated protein kinase (AMPK), and alpha HIF-1α alpha (HIF-1α), KLF2 and nitric oxide synthase (eNOS). Results: Compared with the MCAO group, the survival rate of mice in the EPO group was significantly improved and neurological function was significantly improved (P < 0.01). Western blot results showed that the content of EPO in brain tissue in MCAO group significantly increased compared with sham group. The content of EPO in the brain tissue of mice in the MCAO+EPO treatment group was significantly higher than in that of the MCAO group, which indicates that EPO increased the content of EPO in mouse brain tissue. Compared with the sham group, the protein expression of vascular endothelial growth factor (VEGE) and its receptor (KDR) in brain tissue of the MCAO group significantly decreased. However, the protein expression of VEGE and its receptor KDR in brain tissue of rats treated with MCAO+EPO was significantly higher than in that of the MCAO group. Thus, in this study, EPO was associated with vascular endothelial differentiation after cerebral ischemia in mice. The results of AMPK and KLF2 showed that the expression levels of AMPK and KLF2 in brain tissues of MCAO group mice significantly decreased compared with the sham group. However, the expression levels of AMPK and KLF2 in brain tissues of mice treated with MCAO+EPO were significantly higher than those in the MCAO group. Thus, EPO can activate AMPK and upregulate the expression of the transcription factor KLF2. The protein expression of HIF-1α in the brain tissue of mice in the MCAO group significantly increased compared with the sham group. However, the expression of HIF-1α in mice brain tissues in the MCAO+EPO treatment group was significantly lower than in that of the MCAO group, indicating that EPO was involved in regulating HIF-1α expression. The eNOS results showed that, compared with Sham group, the protein expression of eNOS in brain tissue of MCAO group mice significantly decreased. In the MCAO+EPO treatment group, the protein expression of eNOS was significantly higher in the brain tissue of the mice than in that of the MCAO group, indicating that EPO was involved in the synthesis of NO and promoted the angiogenesis. Conclusion: EPO promotes VEGE and its receptor (KDR) expression and participates in the regulation of HIF-1α and eNOS protein expression through the activation of AMPK-KLF2 signaling pathways to promote new vascular development after cerebral ischemia.

Palavras-chave: EPO, AMPK, KLF-2, angiogenesis
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CITADO POR
  1. Zhang Kai, Wang Junhao, Xi Haiyang, Li Lepeng, Lou Zhaohui, <p>Investigation of Neuroprotective Effects of Erythropoietin on Chronic Neuropathic Pain in a Chronic Constriction Injury Rat Model</p>, Journal of Pain Research, Volume 13, 2020. Crossref

  2. Al-Griw Mohamed A., Alghazeer Rabia O., Awayn Nuri, Shamlan Ghalia, Eskandrani Areej A., Alnajeebi Afnan M., Babteen Nouf A., Alansari Wafa S., Selective adenosine A2A receptor inhibitor SCH58261 reduces oligodendrocyte loss upon brain injury in young rats, Saudi Journal of Biological Sciences, 28, 1, 2021. Crossref

  3. Zheng Wen-Xia, He Wen-Qi, Zhang Qian-Rui, Jia Jin-Xin, Zhao Sheng, Wu Fang-Jian, Cao Xiao-Lu, Baicalin Inhibits NLRP3 Inflammasome Activity Via the AMPK Signaling Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury, Inflammation, 44, 5, 2021. Crossref

  4. Dabravolski Siarhei A., Sukhorukov Vasily N., Kalmykov Vladislav A., Grechko Andrey V., Shakhpazyan Nikolay K., Orekhov Alexander N., The Role of KLF2 in the Regulation of Atherosclerosis Development and Potential Use of KLF2-Targeted Therapy, Biomedicines, 10, 2, 2022. Crossref

  5. Dao Wenxin, Xiao Zhe, Yang Weize, Luo Xiaomin, Xia Hongxia, Lu Zuneng, Knaś Małgorzata, RGS6 Drives Spinal Cord Injury by Inhibiting AMPK Pathway in Mice, Disease Markers, 2022, 2022. Crossref

  6. Ma Yuanyuan, Zhou Zhiyuan, Yang Guo-Yuan, Ding Jing, Wang Xin, The Effect of Erythropoietin and Its Derivatives on Ischemic Stroke Therapy: A Comprehensive Review, Frontiers in Pharmacology, 13, 2022. Crossref

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  8. Arconada-Luque Elena, Jiménez-Suarez Jaime, Pascual-Serra Raquel, Nam-Cha Syong Hyun, Moline Teresa, Cimas Francisco J., Fliquete Germán, Ortega-Muelas Marta, Roche Olga, Fernández-Aroca Diego M., Muñoz Velasco Raúl, García-Flores Natalia, Garnés-García Cristina, Sánchez-Fdez Adrián, Matilla-Almazán Sofía, Sánchez-Arévalo Lobo Víctor J., Hernández-Losa Javier, Belandia Borja, Pandiella Atanasio, Esparís-Ogando Azucena, Ramón y Cajal Santiago, del Peso Luis, Sánchez-Prieto Ricardo, Ruiz-Hidalgo María José, ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology, Cancers, 14, 14, 2022. Crossref

  9. Anderson Sarah, Barthels Derek, Das Hiranmoy, Kruppel-Like Factor 2 and Matrix Metalloproteinases in the Context of Vasculature, in Matrix Pathobiology and Angiogenesis, 12, 2023. Crossref

  10. Guan Yuying, Liu Jia, Gu Yakun, Ji Xunming, Effects of Hypoxia on Cerebral Microvascular Angiogenesis: Benefits or Damages?, Aging and disease, 2022. Crossref

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