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Am J Physiol Lung Cell Mol Physiol 284: L526-L532, 2003; doi:10.1152/ajplung.00131.2002
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Vol. 284, Issue 3, L526-L532, March 2003

Intratracheal gene transfer of decorin reduces subpleural fibroproliferation induced by bleomycin

Minoru Shimizukawa1, Masahito Ebina1, Ko Narumi1, Toshiaki Kikuchi1, Hiroshi Munakata2, and Toshihiro Nukiwa1

1 Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-8575; and 2 Department of 2nd Biochemistry, Kinki University School of Medicine, Osaka 589-8511, Japan

Decorin, a small leucin-rich proteoglycan, is a negative regulator of transforming growth factor-beta , 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 × l09 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.

lung; adenoviral vector; inflammation; in vivo mouse models; usual interstitial pneumonia


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