Glial fibrillary acidic protein (GFAP): modulation by growth factors and its implication in astrocyte differentiation

Abstract

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.

Neuropathology for the Neuroradiologist: Plaques and Tangles

“…18,26 GFAP is a cytoskeletal intermediate protein filament involved in glial cell adhesion, motility, and shape and tends to be upregulated in stress and injury. [27][28][29][30] Fibrous astrocytes also appear in regions of neurofibrillary tangles (NFTs) and neuronal loss. 18 Additionally, activated microglia surround plaques.…”

Cross-talk between neurons and glia: highlights on soluble factors

“…Although neuronal effect mechanisms on astrocytes are still far from being well understood, increasing evidence has been accumulated pointing at neurons as modulators of astrocyte gene expression and differentiation (44)(45)(46)(47). A way to study astrocyte differentiation is by evaluating levels of proteins whose expression patterns vary during astrocyte development such as the intermediate filament glial fibrillary acidic protein (GFAP) (46,47), the enzyme glutamine synthetase (48) and glutamate transporters (49), among others.…”

“…A way to study astrocyte differentiation is by evaluating levels of proteins whose expression patterns vary during astrocyte development such as the intermediate filament glial fibrillary acidic protein (GFAP) (46,47), the enzyme glutamine synthetase (48) and glutamate transporters (49), among others. Two main subtypes of glutamate transporters have been described in glia, i.e., GLAST, with expression predominating at early stages, and GLT-1 whose expression progressively increases with maturity.…”

“…This event was dependent on the brain regional origin of the neurons since cerebral hemisphere neuronal factors were unable to induce the GFAP gene promoter of midbrain and cerebellar astrocytes. Several growth factors are putative candidates in mediating such effect (46). Further analysis of the GFAP gene promoter would contribute to the identification of the neuronal-derived astrocyte differentiation factor.…”

Differential effects of GH and GH-releasing peptide-6 on astrocytes

“…Astrocytes comprise a heterogeneous family of morphologically and functionally distinct cells whose structural plasticity is mostly maintained by a filamentous network mainly consisting of vimentin and glial fibrillary acidic protein (GFAP; Gomes et al 1999a, Järlestedt et al 2010. Astrocytes have a variety of active roles in maintaining normal brain physiology (Barres 1991, Perea & Araque 2005.…”