TGF-beta2 is increased after fetal tracheal occlusion.

BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) accelerates lung growth in normal and hypoplastic fetal lung. The mechanism of accelerated lung growth remains unknown but may be a result of growth factor induction. Previous studies of growth factors induced by tracheal ligation have characterized mRNA rather than protein expression. Although the transforming growth factor-beta (TGF-beta) family participates in normal lung morphogenesis, its role in lung growth after TO is unclear. The authors hypothesize that TGF-beta expression is increased with TO and may contribute to the accelerated lung growth seen after TO. METHODS: Diaphragmatic hernia (DH) was created in 80-day-gestation sheep (n = 6; term, 145) by excising the left diaphragm. At 110 days, the trachea was occluded (n = 4) with a clip. DH controls (n = 2) were not occluded. Fetuses were killed at 139 days, and lung samples were snap frozen for tissue analysis. Non-DH control lungs were harvested from full-term animals (n = 2). TGF-beta mRNA was analyzed by semiquantitative reverse transcriptionase-polymerase chain reaction (RT-PCR). TGF-beta protein was assessed by Western blot analysis. RESULTS: TGF-beta1 mRNA and protein were not increased with tracheal ligation compared with either non-DH or DH controls. TGF-beta2, however, was markedly increased, at both the mRNA and protein level, in ligated lungs compared with nonligated controls. CONCLUSIONS: TGF-beta2 protein, but not TGF-beta1, is increased in the hypoplastic lungs of fetal sheep after tracheal occlusion. Increased TGF-beta2 expression appears to result from increased or prolonged expression of mRNA transcripts. This is the first study to document a change in growth factor protein levels after TO. Increased TGF-beta2 expression may contribute to accelerated lung growth and decreased surfactant production observed after tracheal occlusion.