Fibroblast growth factor 2 (FGF2) and FGF receptor expression in an experimental demyelinating disease with extensive remyelination.
Fibroblast growth factor 2 (FGF2) is an excellent candidate to regulate remyelination based on its proposed actions in oligodendrocyte lineage cell development in conjunction with its involvement in CNS regeneration. To assess the potential for FGF2 to play a role in remyelination, we examined the expression pattern of FGF2 and FGF receptors (FGFRs) in an experimental demyelinating disease with extensive remyelination. Adult mice were intracranially injected with murine hepatitis virus strain A-59 (MHV-A59) to induce focally demyelinated spinal cord lesions that spontaneously remyelinate, with corresponding recovery of motor function. Using kinetic RT-PCR analysis of spinal cord RNA, we found significantly increased levels of FGF2 mRNA transcripts, which peaked during the initial stage of remyelination. Analysis of tissue sections demonstrated that increased levels of FGF2 mRNA and protein were localized within demyelinated regions of white matter, including high FGF2 expression associated with astrocytes. The expression of corresponding FGF receptors was significantly increased in lesion areas during the initial stage of remyelination. In normal and lesioned white matter, oligodendrocyte lineage cells, including progenitors and mature cells, were found to express multiple FGFR types (FGFR1, FGFR2, and/or FGFR3). In addition, in lesion areas, astrocytes expressed FGFR1, FGFR2, and FGFR3. These findings indicate that, during remyelination, FGF2 may play a role in directly regulating oligodendrocyte lineage cell responses and may also act through paracrine or autocrine effects on astrocytes, which are known to synthesize other growth factors and immunoregulatory molecules that influence oligodendrocyte lineage cells.
Messersmith
D J
DJ
Department of Anatomy and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
Murtie
J C
JC
Le
T Q
TQ
Frost
E E
EE
Armstrong
R C
RC
D000818:Animals; D017934:Coronavirus; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006524:Hepatitis, Viral, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D019957:Motor Skills Disorders / Q000139:chemically induced; D009103:Multiple Sclerosis / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*
D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2