Brain-Derived Glia Maturation Factor β Participates in Lung Injury Induced by Acute Cerebral Ischemia by Increasing ROS in Endothelial Cells

作者：Xu, Fei-Fei; Zhang, Zi-Bin; Wang, Yang-Yang; Wang, Ting-Hua^*

来源：Neuroscience Bulletin, 2018, 34(6): 1077-1090.

DOI：10.1007/s12264-018-0283-x

• Glial maturation factor beta
• Acute cerebral ischemia
• Lung injury
• RNA interference
• Pulmonary microvascular endothelial cells
• Reactive oxygen species

Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia (ACI), we established a middle cerebral artery occlusion (MCAO) model in male Sprague-Dawley rats. We focused on glia maturation factor beta (GMFB) based on quantitative analysis of the global rat serum proteome. Polymerase chain reaction, western blotting, and immunofluorescence revealed that GMFB was over-expressed in astrocytes in the brains of rats subjected to MCAO. We cultured rat primary astrocytes and confirmed that GMFB was also up-regulated in primary astrocytes after oxygen-glucose deprivation (OGD). We subjected the primary astrocytes to Gmfb RNA interference before OGD and collected the conditioned medium (CM) after OGD. We then used the CM to culture pulmonary microvascular endothelial cells (PMVECs) acquired in advance and assessed their status. The viability of the PMVECs improved significantly when Gmfb was blocked. Moreover, ELISA assays revealed an elevation in GMFB concentration in the medium after OGD. Cell cultures containing recombinant GMFB showed increased levels of reactive oxygen species and a deterioration in the state of the cells. In conclusion, GMFB is up-regulated in astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing reactive oxygen species. GMFB might thus be an initiator of the lung injury induced by ACI.

• 出版日期2018-12
• 单位四川大学