Airway administration of small silencing RNA oligoneucleotides in mice : transient airspace enlargement induced by VEGF specific blockade in lung.

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We report a readily available model of lung targeted VEGF depletion by airway administration of VEGF small inhibitory RNA oligonucleotides(siRNAs). In the present study, airway administration of VEGF siRNAs mixed in surface active material induced transient air space enlargement in the mouse lung morphologically resembling the previously reported models of pulmonary emphysema. The present model may be useful in dissecting the involvement of VEGF in pulmonary emphysema. Additionally, we found that airway administration of DCI, a combination of dexamethasone, 3'-5'-cyclic adenosine monophosphate, and isobutylmethylxanthine, which has been reported to induce differentiation of type II alveolar cells, attenuated the air space enlargement in this particular model, at least in part through the recovery of lung VEGF expression. We believe that the results of this study have broad implications in the field of respiratory physiology.