Laminin-332 and α3β1 Integrin-Supported Migration of Bronchial Epithelial Cells Is Modulated by Fibronectin
Laminin-332 and α3β1 Integrin-Supported Migration of Bronchial Epithelial Cells Is Modulated by Fibronectin
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DOI：
10.1165/rcmb.2012-0509oc
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发表时间：
2013-11-01
影响因子：
6.4
通讯作者：
Jones, Jonathan C. R.
中科院分区：
文献类型：
--
作者：
Kligys, Kristina;Wu, Yvonne;Jones, Jonathan C. R.
细胞介导的、物理的或化学的损伤的细支气管上皮的修复需要上皮细胞在临时基质上迁移，该临时基质由细胞外基质分子的复合体组成，包括纤维连接蛋白和层粘连蛋白。这些基质分子支持迁移并增强细胞黏附。当细胞与基质粘得太紧时，它们就无法移动；但如果粘得太少，它们就不能产生运动所需的牵引力。因此，我们利用永生化的支气管肺上皮细胞系(BEP2D)和正常人的支气管上皮细胞(NHBE)，研究了层粘连蛋白和纤维连接蛋白在细支气管细胞黏附和迁移中的相对贡献，这两种细胞都组装了层粘连蛋白α3β3伽马2(LM332)/纤维连接蛋白丰富的基质。有趣的是，BEP2D和NHBE细胞在富含LM332的基质上的迁移速度明显快于在纤维连接蛋白上。此外，将纤维连接蛋白添加到LM332基质中会抑制这两种细胞的运动。最后，纤维连接蛋白可增强BEP2D和NHBE细胞对LM332涂层表面的粘附性。这些结果表明，纤维连接蛋白通过促进细支气管细胞与底物的黏附来微调LM332介导的迁移。我们认为，在损伤的呼吸道上皮损伤修复过程中，纤维连接蛋白通过促进细胞与临时基质的稳定相互作用，对层粘连蛋白驱动的上皮细胞的运动起着重要的黏附作用。
The repair of the bronchiolar epithelium damaged by cell-mediated, physical, or chemical insult requires epithelial cell migration over a provisional matrix composed of complexes of extracellular matrix molecules, including fibronectin and laminin. These matrix molecules support migration and enhance cell adhesion. When cells adhere too tightly to their matrix they fail to move; but if they adhere too little, they are unable to develop the traction force necessary for motility. Thus, we investigated the relative contributions of laminin and fibronectin to bronchiolar cell adhesion and migration using the immortalized bronchial lung epithelial cell line (BEP2D) and normal human bronchial epithelial (NHBE) cells, both of which assemble a laminin alpha 3 beta 3 gamma 2 (LM332)/fibronectin-rich matrix. Intriguingly, BEP2D and NHBE cells migrate significantly faster on an LM332-rich matrix than on fibronectin. Moreover, addition of fibronectin to LM332 matrix suppresses motility of both cell types. Finally, fibronectin enhances the adhesion of both BEP2D and NHBE cells to LM332-coated surfaces. These results suggest that fibronectin fine tunes LM332-mediated migration by boosting bronchiolar cell adhesion to substrate. We suggest that, during epithelial wound healing of the injured airway, fibronectin plays an important adhesive role for laminin-driven epithelial cell motility by promoting a stable cellular interaction with the provisional matrix.