Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with β-klotho, an essential coreceptor of FGF21. We further confirmed that human OPCs expressed β-klotho and proliferated in response to FGF21 in vitro. Vascular barrier disruption is a common feature of many CNS disorders; thus, our findings reveal a potentially important role for the peripheral milieu in promoting CNS regeneration.

中文翻译：

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外周来源的FGF21促进中枢神经系统的髓鞘再生

中枢神经系统（CNS）中的脱髓鞘导致严重的神经功能缺损，可以通过自发性髓鞘再生来部分逆转。由于中枢神经系统通过血脑屏障与周围环境隔离，因此髓鞘再生被认为受中枢神经系统微环境控制。但是，在这项工作中，我们发现，在毒素诱导的脱髓鞘的鼠模型中，源自外周组织的因子在损伤后会泄漏到CNS中，并促进髓鞘再生。从机理上讲，主要由胰腺表达的循环成纤维细胞生长因子21（FGF21）的泄漏通过与FGF21的基本共受体β-klotho的相互作用驱动少突胶质细胞前体细胞（OPC）的增殖。我们进一步证实，人OPCs在体外表达β-klotho并响应FGF21增殖。血管屏障的破坏是许多中枢神经系统疾病的共同特征。因此，我们的发现揭示了周围环境在促进中枢神经系统再生中潜在的重要作用。