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

作者:Chen, Wei; Tong, Wusong; Guo, Yijun; He, Bin; Chen, Lei; Yang, Wenjin; Wu, Chenxing; Ren, Dabin; Zheng, Ping*; Feng, Jiugeng*
来源:CNS & Neurological Disorders-Drug Targets, 2018, 17(7): 539-546.
DOI:10.2174/1871527317666180706124602

摘要

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