title: Glucocorticoid receptor β regulates injury-mediated astrocyte activation and contributes to glioma pathogenesis via modulation of β-catenin/TCF transcriptional activity.
abstract: 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 β (GRβ), not GRα, is upregulated and acts as a regulator of gliosis after injury. In addition, our results suggest that GRβ interacts with β-catenin and is a necessary component for proliferation and migration in both injured astrocytes and glioma cells. Further analysis indicated GRβ/β-catenin interaction as a key modulator of astrocyte reactivity through sustained Wnt/β-catenin/TCF signaling in its dominant-negative effect on GRα mediated trans-repression by a GSK-3β-independent manner. These findings expand our knowledge of the mechanism of GRβ 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.
authors.affiliation: Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing Medical University, Wuxi, PR China; Wuxi Clinical Science Research Institute, Wuxi, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Xiufen
authors.initials: X
authors.lastname: Zhang
authors.forename: Zaiwang
authors.initials: Z
authors.lastname: Li
authors.forename: Lingxiao
authors.initials: L
authors.lastname: Deng
authors.forename: Guoqing
authors.initials: G
authors.lastname: Jiao
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Huijun
authors.initials: H
authors.lastname: Mu
authors.forename: Weizhen
authors.initials: W
authors.lastname: Qiao
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
mesh_terms: D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001932:Brain Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000473:pathology*; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D009419:Nerve Tissue Proteins; D011965:Receptors, Glucocorticoid; D051820:TCF Transcription Factors; D051176:beta Catenin; C121943:glucocorticoid receptor beta; D049452:Green Fluorescent Proteins
keywords: Astrocyte activation; Glioma malignancy; Glucocorticoid receptor β; β-Catenin