Erythropoietin promotes Schwann cell migration and assembly of the provisional extracellular matrix by recruiting beta1 integrin to the cell surface.

Erythropoietin promotes Schwann cell migration and assembly of the provisional extracellular matrix by recruiting beta1 integrin to the cell surface.
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DOI:
10.1002/glia.20931
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发表时间:
2010-03
期刊:
影响因子:
6.2
通讯作者:
Campana, W. Marie
Campana, W. Marie
中科院分区:
医学1区
文献类型:
--
作者:
Inoue, Gen;Gaultier, Alban;Li, Xiaoqing;Mantuano, Elisabetta;Richardson, George;Takahashi, Kazuhisa;Campana, W. Marie

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在周围神经损伤中,雪旺细胞经历深刻的表型调节,采用迁移表型并重塑细胞外基质,从而允许轴突再生。神经损伤后雪旺细胞表达促红细胞生成素(Epo)及其受体(EpoR);调节炎症细胞因子的表达并最大限度地缩短神经性疼痛的持续时间。受损周围神经中 Epo 活性的机制仍不完全清楚。在此,我们证明 Epo 在体外促进雪旺细胞在纤连蛋白 (FN) 涂层表面上的迁移。 Epo 还通过 JAK-2 依赖性途径快速将 β1 整合素亚基募集到雪旺细胞表面。尽管含有β1整合素亚基的整合素并不是基础条件下雪旺细胞在FN上粘附或迁移的主要责任,但β1基因沉默阻断了Epo促进细胞迁移的能力。 Epo还在体外和体内诱导雪旺细胞FN表达。 FN在体外被Epo处理的施万细胞组织成不溶性原纤维,并在体内组织成围绕施万细胞的广泛基质。我们的结果支持这样一个模型:Epo 通过影响整合素募集到细胞表面和局部 FN 产生,促进受损周围神经中雪旺细胞迁移和临时细胞外基质的组装。
In peripheral nerve injury, Schwann cells undergo profound phenotypic modulation, adopting a migratory phenotype and remodeling the extracellular matrix so that it is permissive for axonal regrowth. Erythropoietin (Epo) and its receptor (EpoR) are expressed by Schwann cells after nerve injury; regulating inflammatory cytokine expression and minimizing the duration of neuropathic pain. The mechanism of Epo activity in the injured peripheral nerve remains incompletely understood. Herein, we demonstrate that Epo promotes Schwann cell migration in vitro on fibronectin (FN)-coated surfaces. Epo also rapidly recruits β1 integrin subunit to the Schwann cell surface by a JAK-2-dependent pathway. Although β1 integrin subunit-containing integrins were not principally responsible for Schwann cell adhesion or migration on FN under basal conditions, β1 gene-silencing blocked the ability of Epo to promote cell migration. Epo also induced Schwann cell FN expression in vitro and in vivo. The FN was organized into insoluble fibrils by Epo-treated Schwann cells in vitro and into an extensive matrix surrounding Schwann cells in vivo. Our results support a model in which Epo promotes Schwann cell migration and assembly of the provisional extracellular matrix in the injured peripheral nerve by its effects on integrin recruitment to the cell surface and local FN production.
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