EFFECT OF HEPATOCYTE GROWTH FACTOR ON THE FORMATION OF BASEMENT MEMBRANE BY ALVEOLAR EPITHELIAL CELLS IN VITRO
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概要
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Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, endothelial cells, keratinocytes as well as type II alveolar epithelial cells. The secretion of HGF is increased at early phase in acute lung injury. Although HGF is considered to be an important factor for tissue remodeling, little is clarified on the assembly of basement membrane. In this study, we examined the effects of HGF on the basement membrane formation by alveolar epithelial cells in vitro. The integration of basement membrane components by immortalized alveolar type II epithelial cells that were seeded on a fibrillar collagen substratum dose-dependently reduced in the supplement of 0.02ng/ml to 10ng/ml of HGF. Even though the cells could assemble a continuous basement membrane in the presence of entactin containing laminin-1, the supplement of HGF inhibited the formation. Moreover, HGF stimulated the degradation of a basement membrane substratum by the cells. The effects of HGF were attenuated in the presence of TIMP-1. The analysis by zymography and western blot showed that HGF induced the production of MMP-9. These results suggest that the formation of the basement membrane was inhibited by enhanced the degradation of ECM. To simulate a tissue remodeling in vivo, the cells were first cultured in a low density in the presence of 5ng/ml HGF, and next, HGF was switched to TGF-β1. By the serial supplement of HGF and 1ng/ml of TGF-β1, the cells could form a continuous basement membrane whereas the cells with either HGF or TGF-β1 failed. These suggest that the timely production of HGF and TGF-β1 is crucial for normal repair of injured tissue.
- 日本結合組織学会の論文