Keratinocyte Growth Factor Gene Transduction Ameliorates Pulmonary Fibrosis Induced by Bleomycin in Mice

Pulmonary fibrosishas high rates of mortality and morbidity, but there is no established therapy at present. We demonstrate here that bleomycin-induced pulmonary fibrosisin mice is ameliorated by intratracheal administration of keratinocyte growth factor(KGF)-expressing adenovirus vector. Progressive pulmonary fibrosiswas created by continuous subcutaneous administration of 120 mg/kg of bleomycinsubcutaneously using an osmotic pump twice from Day 1 to 7 and Day 29 to 35. The mice initially exhibited subpleural fibrosisand then exhibited advanced fibrosisin the parenchyma of the lungs. These histopathological changes were accompanied by reduced lung compliance (0.041 ± 0.011 versus 0.097 ± 0.004; P < 0.001), reduced messenger expression of surfactant proteins, and reduced KGF messenger expression in the lungs at 4 weeks compared with naive group. Intratracheal instillationof Ad-KGF at 1 week after the first administration of bleomycinincreased KGF mRNA expression in the lungs compared with the fib...