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

Central nervous system (CNS) pericytes have been recognized as an indispensable component of the neurovascular unit. The expression of platelet-derived growth factor receptor beta (PDGFR beta) is markedly increased in CNS pericytes after brain ischemia. It has been elucidated that PDGFR beta, 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 PDGFR beta expression is regulated in pericytes after brain ischemia. We found that basic fibroblast growth factor (bFGF), but neither hypoxia at 1% O-2 nor acidification at pH 6.5, significantly upregulated the PDGFR beta 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 PDGFR beta. 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 PDGFR beta-positive cells in pen-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 PDGFR beta and may enhance PDGFR beta-mediated pericyte functions after brain ischemia. (C) 2015 Elsevier B.V. All rights reserved.