Upregulation of Connexin-43 is Critical for Irradiation-induced Neuroinflammation

Author(s): Wei Chen, Wusong Tong, Yijun Guo, Bin He, Lei Chen, Wenjin Yang, Chenxing Wu, Dabin Ren, Ping Zheng*, Jiugeng Feng*.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 17 , Issue 7 , 2018

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Abstract:

Background: Radiation therapy is widely used for the treatment of pituitary adenomas. Unfortunately, it might raise the risk of ischemic stroke, with neuroinflammation being a major pathological process. Astrocytes are the most abundant cell type in the central nervous system and have been reported for playing important roles in ischemic stroke.

Objective: Here we studied how γ-radiation would introduce astrocytes into a detrimental state for neuroinflammation and provide new theory evidence and target for the clinical management of inflammation- related neural damage after radiation-induced ischemic stroke.

Method: HA-1800 cells were treated with γ-radiation and then the protein and mRNA levels of Connexin (Cx)-43 were evaluated by western and q-PCR. The culture supernatant was collected and the concentrations of the inflammatory factors were determined by ELISA. MiRNA complementary to Cx-43 was designed through the online tools.

Results: Cx-43 is upregulated in the treatment of γ-radiation in astrocytes and γ-radiation introduced the detrimental function of astrocytes: cell viability was reduced while the apoptotic cells were increased. Inflammatory factors like tumor necrosis factor alpha, interferon gamma, interleukin-6, interleukin 1-beta were dramatically up-regulated by the irradiation. MiR-374a rescued irradiation induced Cx-43 up-regulation of astrocytes and eliminated detrimental function triggered by γ-radiation.

Conclusion: Cx-43 expression level may play an important role in the inflammation-related neural damage after irradiation-induced ischemic stroke.

Keywords: Ischemia, Stroke, Cx-43, Astrocytes, MiR-374a, neuroinflammation.

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Article Details

VOLUME: 17
ISSUE: 7
Year: 2018
Page: [539 - 546]
Pages: 8
DOI: 10.2174/1871527317666180706124602
Price: $58

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