Bone morphogenetic protein 9 serves a protective role in response to ischemic‑reperfusion in the brain by promoting ERK activation

Feng,Yinling; Hu,Yida

doi:10.3892/mmr.2017.8253

Bone morphogenetic protein 9 serves a protective role in response to ischemic‑reperfusion in the brain by promoting ERK activation

Authors:
- Yinling Feng
- Yida Hu
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Affiliations: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: December 11, 2017 https://doi.org/10.3892/mmr.2017.8253
Pages: 2845-2852
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the expression and function mechanism of bone morphogenetic protein 9 (BMP9) in cerebral ischemia‑reperfusion (I/R) injuries in vivo and in vitro. A total of 40 Sprague‑Dawley rats were randomly divided into four groups (n=10): i) Normal control; ii) sham surgery group, the procedure without occlusion; iii) I/R group, right middle cerebral artery occlusion (MCAO) followed by reperfusion; and iv) adenoviral vector (Ad)‑BMP9 + I/R group, Ad‑BMP9 intracerebroventricular injection was performed 2 days prior to MCAO. Neurological deficit score and infarct volume were measured at 24 h following reperfusion. To further test the mechanism of BMP9, astrocytes were isolated and treated with Ad‑BMP9, Ad‑BMP9 + extracellular signal‑regulated kinase (ERK) inhibitor PD098059, Ad‑BMP9 + c‑Jun N‑terminal kinase inhibitor SP600125 and Ad‑BMP9 + p38 inhibitor SB203580 for 24 h, followed by undergoing oxygen‑glucose deprivation and reoxygenation (OGD/R) treatment. Cell viability and death were assessed by 3‑(4,5‑dimethylthiazol‑2yl)‑5‑(3‑carboxymethoxyphenyl)‑(4‑sulfophenyl)‑2H‑tetrazolium and lactate dehydrogenase release, respectively. Gene expression was determined by quantitative polymerase chain reaction and western blotting. BMP9 was identified to be upregulated at mRNA and protein levels in cerebral I/R animal and cell models. BMP9 pretreatment significantly reduced the neurological score and infarct volume compared with I/R rats. In astrocytes, overexpression of BMP9 significantly decreased cell death and improved cell viability, an effect which may be mediated by the ERK signaling pathway, as ERK was activated by BMP9 and the use of PD098059 partially reversed the protective effect of BMP9. Pretreatment with BMP‑9 may be a promising treatment option for prevention of cerebral I/R injuries.

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