PDGF Receptor β Signaling in Pericytes Following Ischemic Brain Injury

Koichi      Arimura; Tetsuro      Ago; Masahiro      Kamouchi; Kuniyuki      Nakamura; Koji      Ishitsuka; Junya      Kuroda; Hiroshi      Sugimori; Hiroaki      Ooboshi; Tomio      Sasaki; Takanari      Kitazono

Abstract

Platelet derived growth factor (PDGF)-B plays a neuroprotective role in brain damages, including ischemic stroke. It has been suggested recently that PDGF receptor β (PDGFRβ) expressed in brain pericytes as well as in neurons and astrocytes may mediate the neuroprotective role of PDGF-B. The aims of this study were to elucidate the roles of PDGFRβ signaling in brain pericytes after ischemic stroke. In a rat middle cerebral artery occlusion (MCAO) model, PDGFRβ expression was induced specifically in the pericytes in peri-infarct areas and its level was gradually increased. PDGF-B induced marked phosphorylation of Akt in cultured brain pericytes. Consistently, PDGF-B was upregulated in endothelial cells in per-infarct areas and Akt was strongly phosphorylated in the PDGFRβ-expressing pericytes in periinfarct areas after MCAO. In the cultured pericytes, PDGF-B induced cell growth and anti-apoptotic responses through Akt. Furthermore, PDGF-B significantly increased the expression of nerve growth factor (NGF) and neurotrophin-3 (NT- 3) through Akt in the pericytes. Thus, the PDGFRβ-Akt signaling in brain pericytes may play various important roles leading to neuroprotection after ischemic stroke.

Keywords: angiogenesis, blood brain barrier, endothelial cells, microvascular, PI3K, Cell Signaling Technology, qPCR RT kit, LightCycler, SYBR, neurotrophic factor, Apoptosis, cell growth, ischemic stroke, neuroprotection, neurotrophins, pericyte, PDGF-B, PDGF receptor β