Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia
| Autor: | Jigang Chen, Chunhui Wang, Ming-Kun Yu, Kaiwei Han, Lijun Hou, Zheng Xu, Yan Dong, Rulin Bai, Chenguang Huang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine Angiogenesis Gene Expression Pharmacology Biochemistry Neuroprotection Brain Ischemia Proinflammatory cytokine Rats Sprague-Dawley Brain ischemia Random Allocation 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine medicine Animals Cells Cultured Neuroinflammation business.industry Scavenger Receptors Class A medicine.disease Rats Vascular endothelial growth factor Vascular endothelial growth factor B Vascular endothelial growth factor A Neuroprotective Agents 030104 developmental biology chemistry Microglia business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurochemistry. 142:700-709 |
| ISSN: | 0022-3042 |
| DOI: | 10.1111/jnc.14108 |
| Popis: | Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neurons. However, the role of VEGF in the regulation of ischemic brain injury remains unclear. In this study, rats were subjected to MCAO (middle cerebral artery occlusion) followed by intraperitoneal injection of VEGF165 (10 mg/kg) immediately after surgery and once daily until the day 10. The expression of target genes was assayed using qPCR, western blot and immunofluorescence to investigate the role of VEGF165 in regulating ischemic brain injury. We found that VEGF165 significantly inhibited MCAO-induced up-regulation of Scavenger receptor class A (SR-A) on microglia in a VEGFR1-dependent manner. VEGF165 inhibited lipopolysaccharide (LPS)-induced expression of proinflammatory cytokines IL-1β, tumor necrosis factor alpha (TNF-α) and iNOS in microglia. More importantly, the role of VEGF165 in inhibiting neuroinflammation is partially abolished by SR-A over-expression. SR-A further reduced the protective effect of VEGF165 in ischemic brain injury. These data suggest that VEGF165 suppresses neuroinflammation and ischemic brain injury by inhibiting SR-A expression, thus offering a new target for prevention of ischemic brain injury. |
| Databáze: | OpenAIRE |
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