Idiopathic pulmonary fibrosis (IPF) is a fatal and chronically progressive diffuse parenchymal lung disease that is characterized by varying degrees of fi brosis of the lung parenchyma. 1 Currently, there are few proven, standardized therapies for IPF 2 ; the only viable treatment that has shown survival benefi t for patients with advanced stages of IPF is lung transplantation. [3][4][5][6][7] Nonetheless, the survival benefi t for lung transplantation in patients with IPF is still complicated by signifi cant early mortality rates, especially within the fi rst year (approximately 28%). The 10-year survival rate after lung transplantation is worse for patients with IPF when compared with other diseases, such as idiopathic pulmonary arterial hypertension (PAH), cystic fi brosis, and a 1 -antitrypsin-defi ciency emphysema. 8 Elevated mean pulmonary arterial pressure (mPAP) in patients with IPF has been associated with decreased exercise capacity and worse survival. 9 Higher mPAP was also associated with increased mortality following lung transplantation in a large registry study. 10 One possible explanation for the link between PAH and early mortality after lung transplantation

Altered transforming growth factor (TGF)-b expression levels have been linked to a variety of human respiratory diseases, including bronchopulmonary dysplasia and pulmonary fibrosis. However, a causative role for aberrant TGF-b in neonatal lung diseases has not been defined in primates.Exogenous and transient TGF-b1 overexpression in fetal monkey lung was achieved by transabdominal ultrasound-guided fetal intrapulmonary injection of adenoviral vector expressing TGF-b1 at the second or third trimester of pregnancy. The lungs were then harvested near term, and fixed for histology and immunohistochemistry.Lung hypoplasia was observed where TGF-b1 was overexpressed during the second trimester. The most clearly marked phenotype consisted of severe pulmonary and pleural fibrosis, which was independent of the gestational time point when TGF-b1 was overexpressed. Increased cell proliferation, particularly in a-smooth muscle actin-positive myofibroblasts, was detected within the fibrotic foci. But epithelium to mesenchyme transdifferentiation was not detected. Massive collagen fibres were deposited on the inner and outer sides of the pleural membrane, with an intact elastin layer in the middle. This induced fibrotic pathology persisted even after adenoviralmediated TGF-b1 overexpression was no longer evident.Therefore, overexpression of TGF-b1 within developing fetal monkey lung results in severe and progressive fibrosis in lung parenchyma and pleural membrane, in addition to pulmonary hypoplasia.

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