title: Possible involvement of basic FGF in the upregulation of PDGFRβ in pericytes after ischemic stroke.
abstract: Central nervous system (CNS) pericytes have been recognized as an indispensable component of the neurovascular unit. The expression of platelet-derived growth factor receptor β (PDGFRβ) is markedly increased in CNS pericytes after brain ischemia. It has been elucidated that PDGFRβ, expressed in pericytes and pericyte-derived fibroblast-like cells, plays important roles in the maintenance of the blood-brain barrier (BBB) and in the repair process in infarct areas. The aim of this study was to uncover how the PDGFRβ expression is regulated in pericytes after brain ischemia. We found that basic fibroblast growth factor (bFGF), but neither hypoxia at 1% O2 nor acidification at pH 6.5, significantly upregulated the PDGFRβ expression in human cultured CNS pericytes. SU5402, an inhibitor of FGF receptor (FGFR), and inhibitors of its downstream effectors Akt and Erk abolished the bFGF-induced upregulation of PDGFRβ. On the other hand, acidification significantly upregulated the expression of bFGF, while hypoxia upregulated the expression of FGFR1 in the pericytes. The expression of bFGF and FGFR1 was markedly induced in the ischemic hemisphere after ischemic insult in a middle cerebral artery occlusion stroke model. Immunofluorescent double labeling demonstrated that the expression of bFGF and FGFR1 was co-localized with PDGFRβ-positive cells in peri-infarct areas. Moreover, treatment with bFGF enhanced cell growth and the PDGF-BB-induced migratory activity of cultured pericytes, which were significantly suppressed by SU5402 or Sunitinib, an inhibitor of PDGFR. These data suggested that increased bFGF upregulates the expression of PDGFRβ and may enhance PDGFRβ-mediated pericyte functions after brain ischemia.
authors.affiliation: Department of Internal Medicine, Fukuoka Dental College Medical and Dental Hospital, Tamura, Fukuoka 814-0193, Japan; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan. Electronic address: kunakamu@intmed2.med.kyushu-u.ac.jp.
authors.forename: Kuniyuki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan; Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Arimura
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan; Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Ataru
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tachibana
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yoshikawa
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Makihara
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Wakisaka
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.affiliation: Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kamouchi
authors.affiliation: Department of Internal Medicine, Fukuoka Dental College Medical and Dental Hospital, Tamura, Fukuoka 814-0193, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ooboshi
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan. Electronic address: agou@intmed2.med.kyushu-u.ac.jp.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ago
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D020286:Pericytes / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D020521:Stroke / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; C105686:SU 5402; D016222:Fibroblast Growth Factor 2; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: Basic fibroblast growth factor; Brain ischemia; Pericyte; Platelet-derived growth factor; Stroke