PDGF receptor β signaling in pericytes following ischemic brain injury.
PDGF receptor β signaling in pericytes following ischemic brain injury.
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DOI：
10.2174/156720212799297100
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发表时间：
2012-01
影响因子：
2.1
通讯作者：
K. Arimura;T. Ago;M. Kamouchi;Kuniyuki Nakamura;Koji Ishitsuka;J. Kuroda;H. Sugimori;H. Ooboshi;Tomio Sasaki;T. Kitazono
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文献类型：
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作者：
K. Arimura;T. Ago;M. Kamouchi;Kuniyuki Nakamura;Koji Ishitsuka;J. Kuroda;H. Sugimori;H. Ooboshi;Tomio Sasaki;T. Kitazono
血小板衍生生长因子(PDGF)-B在包括缺血性中风在内的脑损伤中发挥神经保护作用。最近有研究表明，血小板衍生生长因子受体β(β)在脑周细胞、神经元和星形胶质细胞中的表达可能介导了血小板衍生生长因子-B的神经保护作用。本研究的目的是阐明PDGFRβ信号在缺血性卒中后脑周细胞中的作用。在大鼠大脑中动脉闭塞模型中，PDGFRβ在梗死区周围的周细胞中特异性地表达，且表达水平逐渐升高。PDGF-B诱导培养的脑周细胞Akt显著磷酸化。脑缺血后，PDGFB在梗死区的内皮细胞中表达上调，Akt在梗死区表达PDGFFRβ的周细胞中强烈磷酸化。在培养的周细胞中，PDGF-B通过Akt诱导细胞生长和抗凋亡反应。此外，PDGF-B通过Akt显著增加周细胞中神经生长因子(NGF)和神经营养因子-3(NT-3)的表达。因此，脑周细胞中的PDGFRβ-Akt信号可能在缺血性卒中后的神经保护中发挥重要作用。
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.