PDGF and FGF2 regulate oligodendrocyte progenitor responses to demyelination
PDGF and FGF2 regulate oligodendrocyte progenitor responses to demyelination
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DOI：
10.1002/neu.10158
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发表时间：
2003-02-15
期刊：
影响因子：
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通讯作者：
Armstrong, RC
中科院分区：
文献类型：
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作者：
Frost, EE;Nielsen, JA;Armstrong, RC
成人中枢神经系统急性脱髓鞘，由创伤或疾病引起，最初继发髓鞘再生。然而，慢性病变和随后的功能损害是由于髓鞘再生过程的最终失败，如多发性硬化症所见。使用成功的动物模型研究髓鞘再生描述了促进髓鞘再生的一系列事件。这种修复过程的一个普遍特征是少突胶质祖细胞（OPs）在脱髓鞘反应中广泛增殖。为了研究脱髓鞘反应中调控OP增殖的信号，我们使用小鼠肝炎病毒- a59 （MHV-A59）感染成年小鼠，诱导整个脊髓局灶性脱髓鞘，随后自发再脱髓鞘。我们直接从脱髓鞘和再髓鞘脊髓中培养神经胶质细胞，在维持中枢神经系统再髓鞘形成前OP增殖反应显著增强的条件下。我们发现PDGF和FGF2是调节这种增殖反应的重要丝裂原。此外，我们证明了内源性PDGF和FGF2在这些从脱髓鞘中枢组织分离的胶质培养物中具有活性。这些发现与我们之前在MHV-A59病变中PDGF和FGF2配体及相应受体的体内表达增加的证明很好地相关。总之，这些研究支持这些途径在体内作为调节髓鞘再生的关键因素发挥作用的潜力。(C) 2003 Wiley期刊有限公司
Acute demyelination of adult CNS, resulting from trauma or disease, is initially followed by remyelination. However, chronic lesions with subsequent functional impairment result from eventual failure of the remyelination process, as seen in multiple sclerosis. Studies using animal models of successful remyelination delineate a progression of events facilitating remyelination. A universal feature of this repair process is extensive proliferation of oligodendrocyte progenitor cells (OPs) in response to demyelination. To investigate signals that regulate OP proliferation in response to demyelination we used murine hepatitis virus-A59 (MHV-A59) infection of adult mice to induce focal demyelination throughout the spinal cord followed by spontaneous remyelination. We cultured glial cells directly from demyelinating and remyelinating spinal cords using conditions that maintain the dramatically enhanced OP proliferative response prior to CNS remyelination. We identify PDGF and FGF2 as significant mitogens regulating this proliferative response. Furthermore, we demonstrate endogenous PDGF and FGF2 activity in these glial cultures isolated from demyelinated CNS tissue. These findings correlate well with our previous demonstration of increased in vivo expression of PDGF and FGF2 ligand and corresponding receptors in MHV-A59 lesions. Together these studies support the potential of these pathways to function in vivo as critical factors in regulating remyelination. (C) 2003 Wiley Periodicals, Inc.