In vivo gene transfer of an extracellular domain of platelet-derived growth factor beta receptor by the HVJ-liposome method ameliorates bleomycin-induced pulmonary fibrosis.
A number of investigators have reported augmented expression of PDGF in lungs with idiopathic pulmonary fibrosis (IPF) or with other types of pulmonary fibrosis. To accomplish such a regulation of PDGF activity, we constructed an expression plasmid of the extracellular domain of PDGF receptor beta chain (XR), which lacks intracellular tyrosine kinase domain and transmembrane portions, and estimated the therapeutic effects of XR gene transfer through the trachea on bleomycin-induced lung fibrosis of C57BL/6 mice using the hemagglutinating virus of Japan(HVJ)-liposome method. The XR gene transfer ameliorated the increases in the wet weight and hydroxyproline content and the histopathologic changes of the lung induced by bleomycin. These findings suggest that PDGF plays a crucial role in the pathogenesis of pulmonary fibrosis, and that XR gene transfer using the HVJ-liposome method may limit the progression of pulmonary fibrosis.
Yoshida
M
M
Department of Molecular Medicine, Division of Gene Therapy Science, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan. yoshida@imed3.med.osaka-u.ac.jp
Sakuma-Mochizuki
J
J
Abe
K
K
Arai
T
T
Mori
M
M
Goya
S
S
Matsuoka
H
H
Hayashi
S
S
Kaneda
Y
Y
Kishimoto
T
T
D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D019556:COS Cells; D018014:Gene Transfer Techniques; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008081:Liposomes; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018108:Respirovirus / Q000235:genetics
D008081:Liposomes; D001761:Bleomycin; D020797:Receptor, Platelet-Derived Growth Factor beta; D006909:Hydroxyproline