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(Chest. 2001;120:S59.)
© 2001 American College of Chest Physicians

Effect of Hepatocyte Growth Factor on Lung Injury and Development of Clinical Application*

Kenichi Akiyama, MD; M. Miki, MD; K. Narumi, MD; M. Ebina, MD; M. Yaekashiwa, MD; A. Nakamura, MD; T. Nakamura, MD and T. Nukiwa, MD

* From the Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohuko University, Sendai, Japan; and the Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Osaka, Japan.

Correspondence to: Kenichi Akiyama, MD, Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohuku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan

Hepatocyte growth factor (HGF) is a humoral mediator of epithelial-mesenchymal interactions, acting on a variety of epithelial cells. In our previous studies, higher HGF levels were detected in the BAL fluid of patients with pulmonary fibrosis,1 and HGF could prevent the progression of bleomycin-induced lung fibrosis in mice using human recombinant HGF.2 To step up the clinical application of HGF for respiratory diseases, we examined the adenoviral-mediated HGF treatment. While the intratracheal administration of adenoviral vector expressing rat HGF (AdCAG.HGF) yielded high transient HGF expression (312.5 ng/g lung tissue, day 3), adenovirus caused neutrophil alveolitis. In spite of indirect intraperitoneal administration of AdCAG.HGF (6 x 108 pfu) to C57BL/6 mice with bleomycin-induced lung injury, reduced hydroxyproline content (128 ± 5%; n = 5, day 28) resulted in AdCAG.HGF-treated mice, compared with mice treated with adenovirus without complementary DNA insertion (177 ± 9%, p < 0.005). Furthermore, the alveolar apoptotic cells in bleomycin-induced lung injury determined by deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling stain was also reduced by the intraperitoneal administration of AdCAG.HGF (35 ± 4% vs 13 ± 1%; p < 0.05). These results indicate the potential therapeutic effect of HGF for lung injury and fibrosis, and thus await the development of the clinical administration.

Footnotes

Abbreviations: AdCAG.HGF = adenoviral vector expressing rat hepatocyte growth factor; HGF = hepatocyte growth factor

References

  1. Sakai, T, Satoh, K, Matsushina, K, et al (1997) Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with inflammatory chest diseases of the lower respiratory tract: detection by RIA and in situ hybridization. Am J Respir Cell Mol Biol 16,388-397[Abstract]
  2. Yaekashiwa, M, Nakayama, S, Ohnuma, K, et al (1997) Simultaneous or delayed administration of hepatocyte growth factor equally represses the fibrotic changes in murine lung injury induced by bleomycin: a morphologic study. Am J Respir Crit Care Med 156,1937-1944[Abstract/Free Full Text]




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