Glucocorticoid receptor I2 regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of I2-catenin/TCF transcriptional activity

• Published in: Neurobiology of disease Vol. 59; pp. 165 - 176
• Main Authors: Yin, Ying, Zhang, Xiufen, Li, Zaiwang, Deng, Lingxiao, Jiao, Guoqing, Zhang, Bin, Xie, Ping, Mu, Huijun, Qiao, Weizhen, Zou, Jian
• Format: Journal Article
• Language: English
• Published: 01.11.2013
• ISSN: 0969-9961
• DOI: 10.1016/j.nbd.2013.07.013

Astrocytes react to central nervous system (CNS) injury and participate in gliotic responses, imparting negative, as well as positive effects on axonal regeneration. Despite the considerable biochemical and morphological changes astrocytes undergo following insult, and the known influence of steroids on glial activation, details surrounding glucocorticoid receptor expression and activity are lacking. Such mechanistic information is essential for advancing and enhancing therapies in the treatment of CNS injuries. Using an in vitro wound-healing assay, we found glucocorticoid receptor I2 (GRI2), not GRI-, is upregulated and acts as a regulator of gliosis after injury. In addition, our results suggest that GRI2 interacts with I2-catenin and is a necessary component for proliferation and migration in both injured astrocytes and glioma cells. Further analysis indicated GRI2/I2-catenin interaction as a key modulator of astrocyte reactivity through sustained Wnt/I2-catenin/TCF signaling in its dominant-negative effect on GRI- mediated trans-repression by a GSK-3I2-independent manner. These findings expand our knowledge of the mechanism of GRI2 action in promoting astrocyte proliferation and migration following injury and in glioma. This information furthers our understanding the function of glucocorticoid receptor in CNS injury and disease, as well as in the basic biochemical responses astrocytes undergo in response to injury and glioma pathogenesis.