Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly and N-cadherin adhesion.
Membrane-type 1 matrix metalloproteinase regulates fibronectin assembly and N-cadherin adhesion.
复制标题
膜 1 型基质金属蛋白酶调节纤连蛋白组装和 N-钙粘蛋白粘附。
DOI：
10.1016/j.bbrc.2014.06.100
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Sato H.
中科院分区：
文献类型：
--
作者：
Takino T;Yoshimoto T;Nakada M;Li Z;Domoto T;Kawashiri S; Sato H.
纤维连接蛋白基质的形成需要钙粘蛋白粘附产生的细胞骨架张力增加，并受到膜型基质金属蛋白酶（MT1-MMP）的抑制。在将Rat1成纤维细胞与mt1 - mmp沉默的HT1080细胞共培养中，纤连蛋白原纤维从Rat1扩展到HT1080细胞的细胞-基质粘连，并且在Rat1和HT1080细胞之间形成n -钙粘蛋白粘连。对照HT1080细胞与Rat1成纤维细胞接触时，在远离Rat1成纤维细胞的一侧形成细胞-基质粘连，未形成纤维连接蛋白组装和n -钙粘蛋白粘连。利用mt1 - mmp沉默的HT1080细胞，研究了N-cadherin粘附在纤维连接蛋白基质形成中的作用。MT1-MMP敲低可促进HT1080细胞中纤维连接蛋白基质的组装和N-cadherin的粘附，而整合素β1或纤维连接蛋白的双重敲低可消除这一作用。相反，通过敲除N-cadherin或用其中和抗体处理N-cadherin粘附抑制mt1 - mmp沉默细胞中纤维连接蛋白基质的形成。这些结果表明，由MT1-MMP敲低引发的纤维连接蛋白组装导致n -钙粘蛋白粘附增加，这是进一步形成纤维连接蛋白基质的先决条件。
Fibronectin matrix formation requires the increased cytoskeletal tension generated by cadherin adhesions, and is suppressed by membrane-type 1 matrix metalloproteinase (MT1-MMP). In a co-culture of Rat1 fibroblasts and MT1-MMP-silenced HT1080 cells, fibronectin fibrils extended from Rat1 to cell–matrix adhesions in HT1080 cells, and N-cadherin adhesions were formed between Rat1 and HT1080 cells. In control HT1080 cells contacting with Rat1 fibroblasts, cell–matrix adhesions were formed in the side away from Rat1 fibroblasts, and fibronectin assembly and N-cadherin adhesions were not formed. The role of N-cadherin adhesions in fibronectin matrix formation was studied using MT1-MMP-silenced HT1080 cells. MT1-MMP knockdown promoted fibronectin matrix assembly and N-cadherin adhesions in HT1080 cells, which was abrogated by double knockdown with either integrin β1or fibronectin. Conversely, inhibition of N-cadherin adhesions by its knockdown or treatment with its neutralizing antibody suppressed fibronectin matrix formation in MT1-MMP-silenced cells. These results demonstrate that fibronectin assembly initiated by MT1-MMP knockdown results in increase of N-cadherin adhesions, which are prerequisite for further fibronectin matrix formation.