Osteopontin:: A novel axon-regulated Schwann cell gene

Osteopontin:: A novel axon-regulated Schwann cell gene
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DOI:
10.1002/jnr.10099
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发表时间:
2002-01-15
影响因子:
4.2
通讯作者:
Stoll, G
Stoll, G
中科院分区:
医学3区
文献类型:
--
作者:
Jander, S;Bussini, S;Stoll, G

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骨桥蛋白 (OPN) 是一种含有 RGD 的糖蛋白,具有细胞因子样、趋化性和促粘附特性。在伤口愈合过程中,浸润巨噬细胞大量表达 OPN,并参与创伤后组织修复。为了描述在轴切术再生反应中的作用,我们检测了大鼠坐骨神经华勒变性中 OPN 的表达。出乎意料的是,我们发现未受伤的对照神经中的髓鞘雪旺细胞 (SC) 表达了 OPN 的高组成型表达。 OPN mRNA 表达在大鼠 SC 的原代培养物中得到证实。轴突切除后,退化远端神经残端中 SC 表达的 OPN 在损伤后第一天短暂增加,但此后持续下调,在第 14 天达到最低值。侵入轴突神经的巨噬细胞呈 OPN 阴性。在轴索切除术后的后期,SC-OPN 在再生但不是永久横断的神经中重新表达。我们还发现,人类腓肠神经中的髓鞘 SC 表达 OPN,严重的轴突多发性神经病显着减少。综上所述,我们的研究将 OPN 确定为一种受轴突衍生信号调节的新型雪旺细胞基因。浸润巨噬细胞缺乏 OPN 诱导,表明周围神经系统轴突损伤和其他器官系统结构损伤之间的组织修复存在根本差异。 (C) 2002 Wiley-Liss, Inc.
Osteopontin (OPN) is a RGD-containing glycoprotein with cytokine-like, chemotactic, and pro-adhesive properties. During wound healing, OPN is abundantly expressed by infiltrating macrophages and has been implicated in posttraumatic tissue repair. To delineate a role in the regenerative response to axotomy we examined the expression of OPN in Wallerian degeneration of the sciatic nerve in rats. Unexpectedly, we found high constitutive expression of OPN by myelinating Schwann cells (SCs) in uninjured control nerves. OPN mRNA expression was confirmed in primary cultures of rat SCs. Upon axotomy, SC-expressed OPN in the degenerating distal nerve stump transiently increased during the first days after injury, but was continuously downregulated thereafter, reaching its minimum at Day 14. Macrophages invading axotomized nerves were OPN-negative. During late stages after axotomy, SC-OPN was reexpressed in regenerating but not permanently transected nerves. e also found OPN expression by myelinating SCs in human sural nerves with a dramatic reduction in severe axonal polyneuropathies. Taken together, our study identifies OPN as a novel Schwann cell gene regulated by axon-derived signals. The lack of OPN induction in infiltrating macrophages indicates fundamental differences in tissue repair between axonal injury in the peripheral nervous system and structural lesions in other organ systems. (C) 2002 Wiley-Liss, Inc.