Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis

Masaki Watanabe, Masahito Ebina, Frank M. Orson, Akira Nakamura, Kazuo Kubota, Daizo Koinuma, Ken ichi Akiyama, Makoto Maemondo, Shinya Okouchi, Minoru Tahara, Kunio Matsumoto, Toshikazu Nakamura, Toshihiro Nukiwa

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

We examined therapeutic gene transfer of human hepatocyte growth factor (hHGF) to alveolar septa in mouse bleomycin-induced lung fibrosis using macroaggregated albumin-polyethylenimine complex (MAA-PEI). Intravenous administration of MAA-PEI along with 1 μg pCAG.hHGF to C57BL/6 mice increased the uptake of plasmids into alveolar capillary endothelial cells and epithelial cells, prolonged hHGF expression in the lung, and induced a level of hHGF expression equal to that seen with 10 μg of hHGF-expression plasmids alone. The exogenous source of hHGF gene expression increased the endogenous mouse HGF in the lungs and significantly decreased TNF-α, IL-6, and collagen synthesis after bleomycin injury. Because GFP-labeled bone marrow-derived stem cells after bleomycin injury were reduced in number by HGF, the primary mechanism of HGF is likely to be the prevention of apoptosis, as has been suggested by in vitro experiments. This novel HGF gene transfer method to alveolar septa with nonstimulatory MAA-PEI conjugates may have promising clinical applications.

Original languageEnglish
Pages (from-to)58-67
Number of pages10
JournalMolecular Therapy
Volume12
Issue number1
DOIs
Publication statusPublished - 2005 Jul

Keywords

  • Alveolar septa
  • Gene therapy
  • Hepatocyte growth factor
  • Naked plasmids
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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