Hepatocyte growth factor gene transfer into the lung and its' therapeutic effect for lung injury and fibrosis

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In this study, we have examined whether the transfection efficiency can be improved by mechanical ventilation following end tracheal administration of naked-plasmid DNA into lung. Inbred male SD rats were anesthetized and marker gene such as p-CAGGS-Luciferase or p-CAGGS-lucZ was administered into trachea. Ventilation parameters including tidal volume, respiratory rate, degree of PEEP, and respiratory duration were tested to obtain maximum transfection efficiency. The lungs were harvested after 24 hours after gene transfer, and amount of Luciferase was measured by luminometer. Animals administered followed by mechanical ventilation showed increased transfection efficiency comparing the animals that did not treated by mechanical ventilation. X-gal staining to examine the localization of lucZ gene indicated strong staining within the alveolus.Next, we examined the therapeutic effects of gene transfer (Hepatocyte growth factor) in the two different animal models.1) In the bleomycin induced lung fibrosis model, Hepatocyte growth factor gene transfer into lung did not improve the degree of lung fibrosis. On the other hand, mortality increased in the animals that were ventilated.2) The levels of cytokine were analyzed in the LPS induced acute lung injury model. The animals that have higher level of IL-10 showed less lung injury. Thus, we are planning to examine the effect of IL-10 gene transfer into the LPS-induced lung injury model.