Basic fibroblast growth factor promotes the generation of microtubule-associated protein 2-positive cells from microglia.
We recently demonstrated that microglia as multipotential stem cells give rise to microtubule-associated protein 2 (MAP2)-positive and glial fibrillary acidic protein (GFAP)-positive cells and that microglia-derived MAP2-positive cells possess properties of functional neurons. In this study, we investigated the role of fibroblast growth factor (FGF) signaling in the molecular mechanism underlying the generation of microglia-derived MAP2-positive and GFAP-positive cells. Real-time quantitative PCR analyses demonstrated that mRNA levels of a family of three FGF receptors, Fgfr1-3, were upregulated in microglia treated with 70% fetal bovine serum (FBS). Immunocytochemical analyses demonstrated that basic FGF (bFGF) promoted the generation of microglia-derived MAP2-positive and GFAP-positive cells, and the FGF receptor tyrosine kinase inhibitor SU5402 and the MEK inhibitor PD98059 both inhibited this process. Western blot analyses demonstrated that bFGF increased phosphorylated ERK1/2 levels without altering total ERK1/2 levels. These results suggest that bFGF promotes the generation of microglia-derived MAP2-positive and GFAP-positive cells via FGF receptors and the ERK-MAP kinase pathway.
Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. tniidome@pharm.kyoto-u.ac.jp
Tetsuhiro
T
Niidome
Hideki
H
Nonaka
Akinori
A
Akaike
Takeshi
T
Kihara
Hachiro
H
Sugimoto
D000818:Animals; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D017628:Microglia / Q000378:metabolism / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
D008869:Microtubule-Associated Proteins; D011758:Pyrroles; C105686:SU 5402; D016222:Fibroblast Growth Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3