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Basic FGF and FGF receptor 1 are expressed in microglia during experimental autoimmune encephalomyelitis: Temporally distinct expression of midkine and pleiotrophen
Author(s) -
Liu Xia,
Mashour George A.,
Webster Henry Def.,
Kurtz Andreas
Publication year - 1998
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199812)24:4<390::aid-glia4>3.0.co;2-1
Subject(s) - midkine , microglia , fibroblast growth factor , biology , pleiotrophin , experimental autoimmune encephalomyelitis , autocrine signalling , neuroglia , basic fibroblast growth factor , fibroblast growth factor receptor 1 , astrocyte , growth factor , immunology , receptor , central nervous system , endocrinology , inflammation , biochemistry
Heparin‐binding growth factors have been implicated in central nervous system development, regeneration and pathology. To assess the expression pattern and possible function in multiple sclerosis, the heparin‐binding growth factors pleiotrophin (PTN), midkine (MK), basic fibroblast growth factor (FGF‐2) and one of its receptors (FGFR1/ flg) mRNA and protein levels were examined in an experimental autoimmune encephalomyelitis (EAE) model in the Lewis rat. We assessed the time course of expression of PTN, MK and FGF‐2 during EAE and determined the cellular origin of FGF‐2 and FGFR1 in normal spinal cord and during inflammatory demyelination. Basal expression of PTN and MK mRNAs in normal spinal cords was significantly upregulated after induction of EAE. MK expression was upregulated two to threefold correlating with disease progression, whereas PTN expression reached peak levels threefold above basal levels during the clinical recovery period. FGF‐2 mRNA expression was low in normal spinal cord and dramatically increased in correlation with progressive demyelination. FGF‐2 was confined to neurons in normal tissue and shifted dramatically to microglia, paralleling their activation during EAE. Double immunohistochemistry revealed co‐localization of FGF‐2 to activated microglia/ macrophages with strongest expression in the macrophage‐rich perivascular core area and microglial expression at the edges of white and gray matter perivascular regions. FGFR1, like its ligand, was induced in activated macrophages/ microglia. Growth factor expression in demyelinating diseases could serve several functions, e.g., to modulate the activity of microglia/ macrophage in an autocrine fashion, to induce the expression of other factors like insulin‐like growth factor 1 or plasminogen activator, which can effect regeneration or degeneration, respectively, and finally to stimulate directly localized proliferation and/ or regeneration of oligodendrocytes within the lesion area. GLIA 24:390–397, 1998. © 1998 Wiley‐Liss, Inc.