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Pathol Oncol Res. 2019 Jan;25(1):429-435. doi: 10.1007/s12253-018-0471-z. Epub 2018 Sep 18.

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

Author information

1
Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, No.3 Kangfuqian Street, Erqi District, Zhengzhou, 450052, China.
2
Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, No.3 Kangfuqian Street, Erqi District, Zhengzhou, 450052, China. wangjiang066@sina.com.

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.

KEYWORDS:

Ang-(1–7); Blood–brain barrier; Claudin-5; Glioma; ZO-1

PMID:
30229380
DOI:
10.1007/s12253-018-0471-z
[Indexed for MEDLINE]

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