Qin P, Kurpakus M A
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Exp Eye Res. 1998 May;66(5):569-79. doi: 10.1006/exer.1997.0455.
Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) stimulate corneal epithelial cell wound closure. However, the role of these growth factors in regulating corneal epithelial cell motility on basement membrane proteins such as laminin has not been elucidated. In the present study we demonstrate that in an in vitro model of corneal wound healing, TGF alpha has no deleterious effects on the deposition of the laminin-5 isoform into the extracellular matrix structure underlying epithelial cells resurfacing bare collagenous stroma. In primary culture, a population of corneal epithelial cells are stimulated by TGF alpha or EGF to become highly motile. These cells are associated with an endogenously secreted, and extracellularly deposited, 'trail' of laminin-5. The laminin-5 trail is specifically associated with motile cells, as non-motile corneal epithelium exhibiting numerous cell-cell contacts does not display a similar laminin-5 localization pattern. In contrast to these observations, a preparation of laminin-5 known to promote cell spreading, adhesion, and formation of hemidesmosomes, when presented exogenously to cultured corneal epithelial cells, does not stimulate motility. However, a commercially available preparation of laminin derived from human placenta which does not contain laminin-5 does significantly promote the migration of TGF alpha- or EGF-stimulated corneal epithelial cells. From these results, it is hypothesized that endogenously secreted laminin-5 functions to promote migration in corneal epithelial cells which have been treated with TGF alpha or EGF. Exogenously presented laminin-5 does not function similarly, but functions to promote corneal epithelial cell adhesion.
转化生长因子α（TGFα）和表皮生长因子（EGF）可刺激角膜上皮细胞伤口闭合。然而，这些生长因子在调节角膜上皮细胞在诸如层粘连蛋白等基底膜蛋白上的运动方面的作用尚未阐明。在本研究中，我们证明，在角膜伤口愈合的体外模型中，TGFα对层粘连蛋白-5异构体沉积到裸露胶原基质表面上皮细胞下方的细胞外基质结构中没有有害影响。在原代培养中，一群角膜上皮细胞受到TGFα或EGF刺激而变得高度运动。这些细胞与内源性分泌并在细胞外沉积的层粘连蛋白-5“痕迹”相关。层粘连蛋白-5痕迹与运动细胞特异性相关，因为表现出大量细胞间接触的非运动性角膜上皮没有显示出类似的层粘连蛋白-5定位模式。与这些观察结果相反，已知能促进细胞铺展、黏附以及半桥粒形成的层粘连蛋白-5制剂，当外源性给予培养的角膜上皮细胞时，并不会刺激细胞运动。然而，一种不含层粘连蛋白-5的源自人胎盘的市售层粘连蛋白制剂确实能显著促进TGFα或EGF刺激的角膜上皮细胞迁移。根据这些结果，推测内源性分泌的层粘连蛋白-5在促进经TGFα或EGF处理的角膜上皮细胞迁移中起作用。外源性给予的层粘连蛋白-5功能不同，而是起到促进角膜上皮细胞黏附的作用。
