A mechanism of impaired mobility of oligodendrocyte progenitor cells by tenascin C through modification of wnt signaling
A mechanism of impaired mobility of oligodendrocyte progenitor cells by tenascin C through modification of wnt signaling
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DOI：
10.1016/j.febslet.2004.05.022
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发表时间：
2004-06-18
期刊：
影响因子：
3.5
通讯作者：
Miura, M
中科院分区：
文献类型：
--
作者：
Kakinuma, Y;Saito, F;Miura, M
在脱髓鞘疾病中，少突胶质细胞（OLG）祖细胞如何在脱髓鞘区域受到影响的机制仍有待阐明。为了研究其机制的一个方面，我们重点研究了腱生蛋白C通过β-连环蛋白调节祖细胞迁移流动性的作用。通过cDNA消减筛选，我们发现腱生蛋白C在OLG祖细胞（大鼠原代O2 A细胞）中的表达增加。腱生蛋白C抑制OLG祖细胞和CG-4细胞的迁移，并且β-连环蛋白在这些细胞中的粘着斑处积累。这些变化与经典wnt信号的失活有关。过表达的wnt信号拮抗剂Dapper阻止CG-4细胞的迁移。这表明wnt信号的失活是由腱生蛋白C引起的OLG迁移受损的原因。我们的研究结果表明，腱生蛋白C是参与受损的OLG祖细胞的流动性，通过增加的粘附复合物的量，以及防止wnt信号。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
In demyelinating diseases, the mechanisms of how oligodendrocyte (OLG) progenitor cells are affected in the demyelinated area remain to be elucidated. To investigate one aspect of the mechanisms, we focused on the role of tenascin C in regulating the migratory mobility of the progenitor cells via beta-catenin. By cDNA subtraction screening, we found tenascin C expression to be increased in OLG progenitors (rat primary O2A cells). Tenascin C inhibited the migration of OLG progenitors and CG-4 cells, and beta-catenin accumulated at focal adhesions in these cells. These changes were associated with the inactivation of canonical wnt signaling. Overexpression of the wnt-signaling antagonist Dapper prevented the migration of CG-4 cells. This suggests that inactivation of the wnt signal is responsible for impaired migration of OLG caused by tenascin C. Our results suggest that tenascin C is involved in the impaired mobility of OLG progenitor cells through increased amounts of adhesion complex as well as the prevention of wnt signaling. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.