Yamagami Takashi, Pleasure David E, Lam Kit S, Zhou Chengji J
Department of Biochemistry and Molecular Medicine, University of California at Davis, School of Medicine, Sacramento, CA 95817, USA; Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children-Northern California, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children-Northern California, UC Davis School of Medicine, Sacramento, CA 95817, USA.
Biochem Biophys Res Commun. 2018 Feb 19;496(4):1302-1307. doi: 10.1016/j.bbrc.2018.02.004. Epub 2018 Feb 3.
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.
创伤性脊髓损伤（SCI）后，损伤部位可能会形成一种瘢痕，其具有纤维化核心（纤维化瘢痕）和周围的反应性星形胶质细胞（胶质瘢痕）。瘢痕组织被认为是阻碍再生的主要障碍，既是物理屏障，也是轴突再生抑制剂的分泌源。了解瘢痕形成机制以及如何控制它可能会带来有效的SCI治疗方法。在成年转基因小鼠上使用压迫性SCI模型，我们证明经典的Wnt/β-连环蛋白信号报告基因TOPgal（TCF/Lef1-lacZ）阳性细胞在损伤后5天出现在损伤部位，在7天达到峰值，并在14天后减少。使用各种代表性的细胞谱系标记，我们证明，这些短暂的TOPgal阳性细胞是核心瘢痕区域中的一组纤连蛋白（+）；胶质纤维酸性蛋白（-）成纤维细胞样细胞。其中一些细胞具有增殖能力。这些结果表明，Wnt/β-连环蛋白信号可能在创伤性脊髓损伤后的纤维化瘢痕形成中起关键作用。
