Tenascin-C regulates proliferation and migration of cultured astrocytes in a scratch wound assay

Tenascin-C regulates proliferation and migration of cultured astrocytes in a scratch wound assay
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DOI:
10.1016/j.neuroscience.2004.12.028
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发表时间:
2005-01-01
期刊:
影响因子:
3.3
通讯作者:
Hase, T
Hase, T
中科院分区:
医学3区
文献类型:
--
作者:
Nishio, T;Kawaguchi, S;Hase, T

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腱生蛋白-C(TNC)是一种细胞外基质糖蛋白,参与组织形态发生,如胚胎发生、伤口愈合或肿瘤发生。已知星形胶质细胞在CNS中的伤口愈合中起主要作用。为了阐明TNC在星形胶质细胞伤口闭合中的作用,我们研究了培养的星形胶质细胞在划痕实验中的形态学变化,并测量了释放到培养基中的可溶性TNC的含量。我们还定位了TNC mRNA,TNC,胶质细胞酸性蛋白(GFAP),波形蛋白和整合素β 1的表达。创伤后,胶质细胞迅速释放出最大的TNC亚型,并在边界区增殖。随后,它们以单向过程极化,最终向剥蚀区迁移。增殖边缘区细胞和移行前细胞强烈表达TNC mRNA、TNC-、波形蛋白-、GFAP-和整合素β 1样免疫反应性,而移行细胞除前部外表达普遍减少。外源性TNC促进细胞增殖和迁移,而抗TNC或抗整合素β 1抗体的功能阻断则降低了两者。这些结果表明,机械损伤诱导边界星形胶质细胞产生和释放TNC,促进细胞增殖和迁移,通过整合素β 1的自分泌/旁分泌的方式。(c)2005年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Tenascin-C (TNC), an extracellular matrix glycoprotein, is involved in tissue morphogenesis like embryogenesis, wound healing or tumorigenesis. Astrocytes are known to play major roles in wound healing in the CNS. To elucidate the roles of TNC in wound closure by astrocytes, we have examined the morphological changes of cultured astrocytes in a scratch wound assay and measured the content of soluble TNC released into the medium. We have also localized the expression of TNC mRNA, TNC, glial fibrillary acidic protein (GFAP), vimentin and integrin beta 1. After wounding, glial cells rapidly released the largest TNC isoform and proliferated in the border zones. Subsequently, they became polarized with unidirectional processes and finally migrated toward the denuded area. The proliferating border zone cells and pre-migratory cells intensely expressed TNC mRNA, TNC-, vimentin-, GFAP- and integrin beta 1-like immunoreactivity, while the migratory cells showed generally reduced expression except the front. Exogenous TNC enhanced cell proliferation and migration, while functional blocking with anti-TNC or anti-integrin beta 1 antibody reduced both of them. These results suggest that mechanical injury induces boundary astrocytes to produce and release TNC that promotes cell proliferation and migration via integrin beta 1 in an autocrine/paracrine fashion. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.