Transient activation of Wnt/β-catenin signaling reporter in fibrotic scar formation after compression spinal cord injury in adult mice.

Transient activation of Wnt/β-catenin signaling reporter in fibrotic scar formation after compression spinal cord injury in adult mice.
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DOI:
10.1016/j.bbrc.2018.02.004
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发表时间:
2018-02-19
影响因子:
3.1
通讯作者:
Zhou CJ
Zhou CJ
中科院分区:
生物学4区
文献类型:
--
作者:
Yamagami T;Pleasure DE;Lam KS;Zhou CJ

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创伤性脊髓损伤(SCI)后,可能会在损伤部位形成具有纤维化核心(纤维化瘢痕)和周围反应性星形胶质细胞(神经胶质瘢痕)的瘢痕。瘢痕组织被认为是阻止再生的主要障碍,既作为物理屏障又作为轴突再生抑制剂的分泌来源。了解疤痕形成的机制以及如何控制它可能会导致有效的SCI治疗。使用成年转基因小鼠的压缩-SCI模型,我们证明了典型的Wnt/β-catenin信号报告基因TOPgal(TCF/Lef 1-lacZ)阳性细胞在损伤部位出现5天,在7天达到峰值,并在损伤后14天减少。使用各种代表性的细胞谱系标记物,我们证明,这些短暂的TOPgal阳性细胞是一组纤连蛋白(+);GFAP(-)成纤维细胞样细胞在核心瘢痕区域。其中一些是增殖性的。这些结果表明Wnt/β-catenin信号通路可能在创伤性脊髓损伤后纤维化瘢痕形成中起关键作用。
After traumatic spinal cord injury (SCI), a scar may form with a fibrotic core (fibrotic scar) and surrounding reactive astrocytes (glial scar) at the lesion site. The scar tissue is considered a major obstacle preventing regeneration both as a physical barrier and as a source for secretion of inhibitors of axonal regeneration. Understanding the mechanism of scar formation and how to control it may lead to effective SCI therapies. Using a compression-SCI model on adult transgenic mice, we demonstrate that the canonical Wnt/β-catenin signaling reporter TOPgal (TCF/Lef1-lacZ) positive cells appeared at the lesion site by 5 days, peaked on 7 days, and diminished by 14 days post injury. Using various representative cell lineage markers, we demonstrate that, these transiently TOPgal positive cells are a group of Fibronectin(+);GFAP(−) fibroblast-like cells in the core scar region. Some of them are proliferative. These results indicate that Wnt/β-catenin signaling may play a key role in fibrotic scar formation after traumatic spinal cord injury.
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