title: TGF-beta2 is increased after fetal tracheal occlusion.
abstract: OBJECTIVE
  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.
authors.affiliation: The Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, and the University of Pennsylvania School of Medicine, 19104, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Quinn
authors.forename: K G
authors.initials: KG
authors.lastname: Sylvester
authors.forename: Y
authors.initials: Y
authors.lastname: Kitano
authors.forename: Y
authors.initials: Y
authors.lastname: Kitano
authors.forename: K W
authors.initials: KW
authors.lastname: Liechty
authors.forename: B P
authors.initials: BP
authors.lastname: Jarrett
authors.forename: N S
authors.initials: NS
authors.lastname: Adzick
authors.forename: A W
authors.initials: AW
authors.lastname: Flake
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006548:Hernia, Diaphragmatic / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D014132:Trachea / Q000196:embryology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta