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1 Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA
2 Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA
3 Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Department of Pathology, University of Colorado Health Sciences Center, Denver, CO, USA
4 Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA; Department of Immunology, University of Colorado Health Sciences Center, Denver, CO, USA
5 Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA; Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Department of Immunology, University of Colorado Health Sciences Center, Denver, CO, USA
* To whom correspondence should be addressed. E-mail: richesd{at}njc.org.
Insulin-like growth factor-I (IGF-I) has been implicated in post-natal alveolar development, pulmonary fibrosis and non-small cell lung cancer. To further investigate the role of IGF-I, we created a line of transgenic mice in which alveolar type II epithelial cells express human IGF-IA under the control of the SP-C promoter. We determined the effect of pulmonary over-expression of human IGF-IA on i) pulmonary inflammation and fibrosis in response to intra-tracheal instillation of bleomycin, ii) pre-malignant pulmonary adenomatous hyperplasia and iii) adenoma formation. Transgenic expression of human IGF-IA had no effect on baseline gross lung pathology, cellularity of bronchoalveolar lavage or total lung collagen content. In addition, there were no significant differences between transgenic mice and non-transgenic littermate controls in the development of pulmonary inflammation or pulmonary fibrosis in response to intratracheal bleomycin instillation. However, pulmonary expression of human IGF-IA in older mice (> 12 months) significantly increased the incidence of pre-malignant adenomatous hyperplastic lesions compared to littermate controls without affecting adenoma formation. These findings suggest that increased expression of human IGF-IA in alveolar airspaces does not affect the development of pulmonary fibrosis, but promotes pre-malignant changes in the alveolar epithelium.
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