Ionizing radiation modulates vascular endothelial growth factor expression through STAT3 signaling pathway in rat neonatal primary astrocyte cultures

Autor: Yilin Wang, Yunqian Chang, Bing He, Guijuan Zhou, Jianghua Huang, Zijian Xiao, Yangzhi Xie, Yan Xu, Rundong Ma, Lin Wu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
STAT3 Transcription Factor
Vascular Endothelial Growth Factor A
medicine.medical_treatment
050105 experimental psychology
Stat3 Signaling Pathway
lcsh:RC321-571
Rats
Sprague-Dawley
03 medical and health sciences
Behavioral Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Radiation
Ionizing
Animals
Medicine
0501 psychology and cognitive sciences
STAT3
radiation‐induced brain injury
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Original Research
Cerebral Cortex
Glial fibrillary acidic protein
biology
vascular endothelial growth factor
business.industry
05 social sciences
astrocytes
Rats
Vascular endothelial growth factor
medicine.anatomical_structure
Cytokine
chemistry
glial fibrillary acidic protein
biology.protein
Cancer research
STAT protein
signal transducer and activator of transcription 3
Signal transduction
business
030217 neurology & neurosurgery
Signal Transduction
Astrocyte
Zdroj: Brain and Behavior, Vol 10, Iss 4, Pp n/a-n/a (2020)
Brain and Behavior
ISSN: 2162-3279
Popis: Background and Purpose Radiation‐induced brain injury (RBI) usually occurs six months to three years after irradiation, often shows cognitive dysfunction, epilepsy, and other neurological dysfunction. In severe cases, it can cause a wide range of cerebral edema, even herniation. It seriously threatens the survival of patients and their quality of life, and it becomes a key factor in limiting the radiation dose and lowering the therapeutic efficacy in recent years. Therefore, studying the pathogenesis of RBI and exploring new therapeutic targets are of great significance. Methods In our study, we observed the activation and secretory function in astrocytes as well as the intracellular signal transducer and activator of transcription 3 (STAT3) signal transduction pathway activation status after exposing different doses of X‐ray irradiation by using MTT, Immunocytologic analysis, and Western blot analysis. Further, we used the same way to explore the role of vascular endothelial growth factor (VEGF) in signal transduction pathways playing in the activation of astrocytes after irradiating through the use of specificInhivascular endothelial growth factorbitors of STAT3. Results Ast can be directly activated, reactive hyperplasia and hypertrophy, the expression of the activation marker glial fibrillary acidic protein is increased, and the expression of vascular endothelial growth factor (VEGF) in the cells is increased, which may lead to RBI. After the addition of STAT3 pathway inhibitor, most of the Ast radiation activation was suppressed, and the expression of high‐level expression of VEGF decreased after irradiation. Conclusion Our findings demonstrated that X‐ray irradiation directly induced the activation of astrocytes in a persistent manner and X‐ray irradiation activated STAT3 signaling pathway. As the same time, we found that X‐ray irradiation induced the activation of astrocytes and secretion cytokine. The STAT3 signaling pathway may participate in the pathogenesis of radiation‐induced brain injury.
In this work, we found the changes of vascular endothelial growth factor(VEGF) and glial fibrillary acidic protein (GFAP), and the signal transducer and activator of transcription 3(STAT3) signaling pathways involved in astrocytes exposure to X‐rays may be instructive for improving the efficiency of radiation therapy while reducing damage to normal brain tissue.
Databáze: OpenAIRE
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