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Am J Physiol Lung Cell Mol Physiol 286: L939-L946, 2004. First published December 12, 2003; doi:10.1152/ajplung.00238.2002
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Hepatocyte growth factor inhibits the formation of the basement membrane of alveolar epithelial cells in vitro

Akiko Furuyama1 and Katsumi Mochitate2

1Inhalation Toxicology Team and 2Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan

Submitted 19 July 2002 ; accepted in final form 9 December 2003

Hepatocyte growth factor (HGF) is a pulmotrophic factor for the regeneration of injured pulmonary tissue. We investigated the role of HGF in basement membrane formation during wound healing by immortalized alveolar type II epithelial cells that could form a continuous basement membrane when they were cultured on collagen fibrils in the presence of entactin-contaminated laminin-1. Cells cultured with 5.0 ng/ml HGF neither formed a continuous basement membrane on collagen fibrils nor maintained a continuous basement membrane architecture on a basement membrane substratum. The cells showed increased secretion of matrix metalloproteinase-9 and urokinase-type plasminogen activator, and the HGF-induced inhibition of basement membrane formation was attenuated by addition of 200 ng/ml tissue inhibitor of matrix metalloproteinase-1. Cells sequentially exposed to HGF and 1.0 ng/ml transforming growth factor-{beta}1 had enhanced basement membrane formation compared with those receiving these reagents in the reverse order or concurrently. HGF simultaneously stimulated proliferation and migration of the cells so that it advanced wound closure on the basement membrane substratum. The present results indicate that the role of HGF in wound healing is the stimulation of reepithelization, but this factor may also contribute to the degradation of the basement membrane.

wound healing; matrix metalloproteinase-9; urokinase-type plasminogen activator; lamina densa; transforming growth factor-{beta}1


Address for reprint requests and other correspondence: A. Furuyama, Inhalation Toxicology Team, PM2.5 & DEP Research Project, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan (E-mail: kawagoe{at}nies.go.jp).




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L. Plantier, S. Marchand-Adam, J. Marchal-Somme, G. Leseche, M. Fournier, M. Dehoux, M. Aubier, and B. Crestani
Defect of hepatocyte growth factor production by fibroblasts in human pulmonary emphysema
Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L641 - L647.
[Abstract] [Full Text] [PDF]


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