Coordination of fibroblast growth factor receptor 1 (FGFR1) and fibroblast growth factor-2 (FGF-2) trafficking to nuclei of reactive astrocytes around cerebral lesions in adult rats.
Traumatic injury to the adult central nervous system initiates a cascade of cellular and trophic events, culminating in the formation of a reactive gliotic scar through which transected axons fail to regenerate. Levels of fibroblast growth factor-2 (FGF-2), a potent gliogenic and neurotrophic factor, together with its full-length receptor, FGF receptor 1 (FGFR1) are coordinately and significantly increased postinjury in both nuclear and cytoplasmic fractions of extracted cerebral cortex biopsies after a penetrant injury. FGFR1 is colocalized with FGF-2 in the nuclei of reactive astrocytes, and here FGF-2 is associated with nuclear euchromatin. This study unequivocally demonstrates coordinate up-regulation and trafficking of FGF-2 and full-length FGFR1 to the nucleus of reactive astrocytes in an in vivo model of brain injury, thereby implicating a role in nuclear activity for these molecules. However, the precise contribution of nuclear FGF-2/FGFR1 to the pathophysiological response of astrocytes after injury is undetermined.
Clarke
W E
WE
Department of Medicine, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Berry
M
M
Smith
C
C
Kent
A
A
Logan
A
A
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D022041:Euchromatin / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005911:Gliosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D020197:Head Injuries, Penetrating / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D015854:Up-Regulation
D022041:Euchromatin; D020033:Protein Isoforms; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1