Intratracheal gene transfer of decorin reduces subpleural fibroproliferation induced by bleomycin

Minoru Shimizukawa, Masahito Ebina, Ko Narumi, Toshiaki Kikuchi, Hiroshi Munakata, Toshihiro Nukiwa

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Decorin, a small leucin-rich proteoglycan, is a negative regulator of transforming growth factor-β but the antifibrotic effect of decorin gene transfer has not been examined in a mouse model of usual interstitial pneumonia (UIP). We constructed a replication-defective recombinant adenovirus harboring human decorin gene (AdCMV.DC) and administered 1 x 109 plaque-forming units of AdCMV.DC intratracheally or intravenously to C57BL/6 mice with intraperitoneal injection of bleomycin, which induces a subpleural fibroproliferation, mimicking UIP, by day 28. Only intratracheal administration of AdCMV.DC increased decorin mRNA expression in the lung and decreased the hydroxyproline content augmented in bleomycin-induced pulmonary fibrosis (1.13 ± 0.02 to 0.96 ± 0.02, P = 0.006). In contrast, intravenous administration of AdCMV.DC increased the decorin expression only in the liver, but not in the lung, and without reducing lung fibrosis. These results indicate that adenoviral decorin gene transfer is effective only by direct administration to fibrosing lungs.

Original languageEnglish
Pages (from-to)L526-L532
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume284
Issue number3 28-3
Publication statusPublished - 2003 Mar 1

Keywords

  • Adenoviral vector
  • In vivo mouse models
  • Inflammation
  • Lung
  • Usual interstitial pneumonia

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Shimizukawa, M., Ebina, M., Narumi, K., Kikuchi, T., Munakata, H., & Nukiwa, T. (2003). Intratracheal gene transfer of decorin reduces subpleural fibroproliferation induced by bleomycin. American Journal of Physiology - Lung Cellular and Molecular Physiology, 284(3 28-3), L526-L532.