RESUMO
Intermediate filament (IF) proteins constitute an extremely large multigene family of developmentally and tissue-regulated cytoskeleton proteins abundant in most vertebrate cell types. Astrocyte precursors of the CNS usually express vimentin as the major IF. Astrocyte maturation is followed by a switch between vimentin and glial fibrillary acidic protein (GFAP) expression, with the latter being recognized as an astrocyte maturation marker. Levels of GFAP are regulated under developmental and pathological conditions. Upregulation of GFAP expression is one of the main characteristics of the astrocytic reaction commonly observed after CNS lesion. In this way, studies on GFAP regulation have been shown to be useful to understand not only brain physiology but also neurological disease. Modulators of GFAP expression include several hormones such as thyroid hormone, glucocorticoids and several growth factors such as FGF, CNTF and TGF beta, among others. Studies of the GFAP gene have already identified several putative growth factor binding domains in its promoter region. Data obtained from transgenic and knockout mice have provided new insights into IF protein functions. This review highlights the most recent studies on the regulation of IF function by growth factors and hormones.
Assuntos
Astrócitos , Proteína Glial Fibrilar Ácida/metabolismo , Substâncias de Crescimento , Proteínas Morfogenéticas Ósseas , Diferenciação Celular , Sistema Nervoso Central , Fatores de Crescimento de Fibroblastos , Fator de Crescimento Transformador beta , Fator de Necrose Tumoral alfa , VimentinaRESUMO
In order to investigate the influence of neuron-glia interaction on astrocyte differentiation, we used a transgenic mouse bearing part of the gene promoter of the astrocytic maturation marker GFAP linked to the beta-galactosidase (beta-gal) reporter gene. Addition of embryonic cerebral hemisphere (CH) neurons to transgenic CH astrocyte monolayers increased by 50-60% beta-gal positive cell number. Such event was dependent on the brain regional origin of the neurons and was followed by an arrest of astrocytes from the cell cycle and induction of glial differentiation. Time-course assays demonstrated that maximum effect was observed after 24 h of coculture. Addition of conditioned medium (CM) derived from CH neurons also increased beta-gal positive CH astrocytic cell number. However, such CM had no effect on midbrain and cerebellum astroglia. Together, these data suggest that neurons secrete brain region-specific soluble factors which induce GFAP gene promoter, as measured by beta-gal expression, thus suggesting that neuron-glia interaction might induce the astrocytic differentiation program.
Assuntos
Astrócitos/fisiologia , Proteína Glial Fibrilar Ácida/genética , Neurônios/fisiologia , Regiões Promotoras Genéticas/fisiologia , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Encéfalo/fisiologia , Comunicação Celular/fisiologia , Ciclo Celular/fisiologia , Células Cultivadas , Difusão , Expressão Gênica/fisiologia , Regulação da Expressão Gênica/fisiologia , Óperon Lac/fisiologia , Camundongos , Camundongos Transgênicos/genética , Neuroglia/fisiologia , Neurônios/metabolismo , Fatores de TempoRESUMO
Intermediate filament (IF) proteins constitute an extremely large multigene family of developmentally and tissue-regulated cytoskeleton proteins abundant in most vertebrate cell types. Astrocyte precursors of the CNS usually express vimentin as the major IF. Astrocyte maturation is followed by a switch between vimentin and glial fibrillary acidic protein (GFAP) expression, with the latter being recognized as an astrocyte maturation marker. Levels of GFAP are regulated under developmental and pathological conditions. Upregulation of GFAP expression is one of the main characteristics of the astrocytic reaction commonly observed after CNS lesion. In this way, studies on GFAP regulation have been shown to be useful to understand not only brain physiology but also neurological disease. Modulators of GFAP expression include several hormones such as thyroid hormone, glucocorticoids and several growth factors such as FGF, CNTF and TGFß, among others. Studies of the GFAP gene have already identified several putative growth factor binding domains in its promoter region. Data obtained from transgenic and knockout mice have provided new insights into IF protein functions. This review highlights the most recent studies on the regulation of IF function by growth factors and hormones