Possible involvement of basic FGF in the upregulation of PDGFRβ in pericytes after ischemic stroke

Kuniyuki Nakamura, Koichi Arimura, ataru nishimura, Masaki Tachibana, Yoji Yoshikawa, Noriko Makihara, Yoshinobu Wakisaka, Junya Kuroda, Masahiro Kamouchi, Hiroaki Ooboshi, Takanari Kitazono, Tetsuro Ago

研究成果: ジャーナルへの寄稿記事

14 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)98-108
ページ数11
ジャーナルBrain Research
1630
DOI
出版物ステータス出版済み - 1 1 2016

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Platelet-Derived Growth Factor Receptors
Pericytes
Fibroblast Growth Factor 2
Up-Regulation
Stroke
Brain Ischemia
Central Nervous System
Middle Cerebral Artery Infarction
Fibroblast Growth Factor Receptors
Blood-Brain Barrier
Fibroblasts
Maintenance

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

これを引用

Possible involvement of basic FGF in the upregulation of PDGFRβ in pericytes after ischemic stroke. / Nakamura, Kuniyuki; Arimura, Koichi; nishimura, ataru; Tachibana, Masaki; Yoshikawa, Yoji; Makihara, Noriko; Wakisaka, Yoshinobu; Kuroda, Junya; Kamouchi, Masahiro; Ooboshi, Hiroaki; Kitazono, Takanari; Ago, Tetsuro.

:: Brain Research, 巻 1630, 01.01.2016, p. 98-108.

研究成果: ジャーナルへの寄稿記事

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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.",
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AU - Arimura, Koichi

AU - nishimura, ataru

AU - Tachibana, Masaki

AU - Yoshikawa, Yoji

AU - Makihara, Noriko

AU - Wakisaka, Yoshinobu

AU - Kuroda, Junya

AU - Kamouchi, Masahiro

AU - Ooboshi, Hiroaki

AU - Kitazono, Takanari

AU - Ago, Tetsuro

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