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Suppression of Angiotensin-(1–7) on the Disruption of Blood-Brain Barrier in Rat of Brain Glioma

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Pathology & Oncology Research

Abstract

Glioblastoma multiforme (GBM) is the most primary brain tumor, specially characterized with the damage of blood-brain barrier (BBB). The Ang-(1–7) was proven to have an inhibitory effect on glioblastoma growth. However, its role on blood–brain barrier (BBB) and the underlying molecular mechanism remains unclear. In this study, Ang-(1–7) significantly relieved the damage of blood-brain barrier in rats with intracranial U87 gliomas as evaluated by magnetic resonance imaging (MRI). Furthermore, its treatment attenuated BBB permeability, tumor growth and edema formation. Similarly, Ang-(1–7) also decreased U87 glioma cells barrier permeability in vitro. Further analysis showed that Ang-(1–7) could effectively restore tight junction protein (claudin-5 and ZO-1) expression levels both in rats and U87 glioma cells by affecting the activation of JNK pathway. SP600125, an inhibitor of JNK, significantly enhanced the expression of Claudin-5 and ZO-1, and decreased the disruption of BBB and enhanced the efficiency of Ang-(1–7) in glioma rats. Taken together, this study demonstrated a protective role of Ang-(1–7) in glioma-induced blood-brain barrier damage by regulating tight junction protein expression. Accordingly, Ang-(1–7) may become a promising therapeutic agent against glioma.

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Fig. 1: Ang-(1–7) abates the damage of blood-brain barrier in glioma rats.
Fig. 2: Ang-(1–7) relieves the disruption of barrier function in endothelial cells.
Fig. 3: Ang-(1–7) increases the expression of tight junction proteins.
Fig. 4: Ang-(1–7) increased the expression of Claudin-5 and ZO-1 by regulating JNK pathway.

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Acknowledgments

Xiaohui Li and Xinjun Wang designed the study. Xiaohui Li, Jingwei Xie and Bo Liang performed the research and wrote the paper. Jianheng Wu performed the research. Xinjun Wang accepted full responsibility for the work.

This research was supported by the Key project of Science and Technology Research of Education Department of Henan province (14A320078).

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Authors and Affiliations

  1. Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, No.3 Kangfuqian Street, Erqi District, Zhengzhou, 450052, China

    Xiaohui Li, Xinjun Wang, Jingwei Xie, Bo Liang & Jianheng Wu

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  1. Xiaohui Li
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  2. Xinjun Wang
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  3. Jingwei Xie
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Correspondence to Xinjun Wang.

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Li, X., Wang, X., Xie, J. et al. Suppression of Angiotensin-(1–7) on the Disruption of Blood-Brain Barrier in Rat of Brain Glioma. Pathol. Oncol. Res. 25, 429–435 (2019). https://doi.org/10.1007/s12253-018-0471-z

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  • DOI: https://doi.org/10.1007/s12253-018-0471-z

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