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 lun gs with idiopathic pulmonary fibrosis (IPF) or with other types of pulmonar y fibrosis. To accomplish such a regulation of PDGF activity, we constructe d an expression plasmid of the extracellular domain of PDGF receptor beta c hain (XR), which lacks intracellular tyrosine kinase domain and transmembra ne portions, and estimated the therapeutic effects of XR gene transfer thro ugh the trachea on bleomycin-induced lung fibrosis of C57BL/6 mice using th e hemagglutinating virus of Japan(HVJ)-liposome method. The XR gene transfe r ameliorated the increases in the wet weight and hydroxyproline content an d the histopathologic changes of the lung induced by bleomycin. These findi ngs suggest that PDGF plays a crucial role in the pathogenesis of pulmonary fibrosis, and that XR gene transfer using the HVJ-liposome method may limi t the progression of pulmonary fibrosis.