TY - JOUR
T1 - Possible involvement of basic FGF in the upregulation of PDGFRβ in pericytes after ischemic stroke
AU - Nakamura, Kuniyuki
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
N1 - Funding Information:
This study was supported in part by Grants-in-Aid for Scientific Research (C) ( 25461134 ) (to J.K.), (C) (26461145) (to T.A.), (C) (26462163) (to Y.W.), (C) (23591262) (to H.O.) and Grants-in-Aid for Young Scientists (B) ( 26861169 ) (to K.N.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan , a grant from Kaibara Morikazu Medical Science Promotion Foundation, Japan (to K.N.), a grant from SENSHIN Medical Research Foundation, Japan (to T.A.), a grant from the Takeda Science Foundation, Japan (to T.A. and J.K.) and the Innovation Center for Medical Redox Navigation (to T.A.).
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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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U2 - 10.1016/j.brainres.2015.11.003
DO - 10.1016/j.brainres.2015.11.003
M3 - Article
C2 - 26569132
AN - SCOPUS:84962216712
SN - 0006-8993
VL - 1630
SP - 98
EP - 108
JO - Molecular Brain Research
JF - Molecular Brain Research
ER -