TGF-beta 2 is increased after fetal tracheal occlusion

Background/Purpose: Fetal tracheal occlusion (TO) accelerates lung growth i n normal and hypoplastic fetal lung. The mechanism of accelerated lung grow th 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 facto r-beta (TGF-beta) family participates in normal lung morphogenesis, its rol e 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 w as occluded (n = 4) with a clip. DH controls (n = 2) were not occluded. Fet uses 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 Wester n blot analysis. Results: TGF-beta 1 mRNA and protein were not increased with tracheal ligat ion compared with either non-DH or DH controls. TGF-beta 2, however, was ma rkedly increased, at both the mRNA and protein level, in ligated lungs comp ared with nonligated controls. Conclusions: TGF-beta 2 protein, but not TGF-beta 1, is increased in the hy poplastic lungs of fetal sheep after tracheal occlusion. Increased TGF-beta 2 expression appears to result from increased or prolonged expression of m RNA transcripts. This is the fi rst study to document a change in growth fa ctor protein levels after TO. Increased TGF-beta 2 expression may contribut e to accelerated lung growth and decreased surfactant production observed a fter tracheal occlusion. Copyright (C) 1999 by W.B. Saunders Company.