Zahm J M, Debordeaux C, Raby B, Klossek J M, Bonnet N, Puchelle E
INSERM U514, IFR53, Reims, France.
J Cell Physiol. 2000 Dec;185(3):447-53. doi: 10.1002/1097-4652(200012)185:3<447::AID-JCP16>3.0.CO;2-D.
Cell migration is the earliest mechanism involved in the wound repair process of the respiratory epithelium and could be potentially enhanced by growth factors. In the present work, we investigated the localisation of the hepatocyte growth factor (HGF) receptor (c-Met) during wound repair and evaluated the effect of recombinant HGF (rHGF) on cell migration by using an in vitro model of airway epithelial wound repair. By using immunohistochemical methods, we observed that the immunoreactivity of the c-Met proto-oncogene was increased in epithelial cells engaged in the process of tissue repair. The incubation of wounded cultures with increasing concentrations of rHGF (0.2, 2, 20, and 200 ng/ml) induced a significant (P < 0.02) dose-dependent effect on the wound repair index, with a maximum effect produced at 20 ng/ml (+31.3%). The cell migration speed reached 50.2 micrometer/h at this concentration, compared to 20.4 micrometer/h in the absence of rHGF. No significant effect on cell proliferation was observed in the repairing area in the presence of rHGF. These results suggest that rHGF is able to improve the wound repair process of the airway epithelium by increasing cell migration.
细胞迁移是呼吸道上皮伤口修复过程中最早涉及的机制，并且可能会被生长因子潜在增强。在本研究中，我们调查了肝细胞生长因子（HGF）受体（c-Met）在伤口修复过程中的定位，并通过使用气道上皮伤口修复的体外模型评估了重组HGF（rHGF）对细胞迁移的影响。通过免疫组织化学方法，我们观察到在参与组织修复过程的上皮细胞中，c-Met原癌基因的免疫反应性增加。用浓度递增的rHGF（0.2、2、20和200 ng/ml）孵育受伤的培养物，对伤口修复指数产生了显著的（P < 0.02）剂量依赖性效应，在20 ng/ml时产生最大效应（+31.3%）。在此浓度下，细胞迁移速度达到50.2微米/小时，而在无rHGF时为20.4微米/小时。在rHGF存在的情况下，在修复区域未观察到对细胞增殖的显著影响。这些结果表明，rHGF能够通过增加细胞迁移来改善气道上皮的伤口修复过程。
