TGF-beta2 is increased after fetal tracheal occlusion.
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.
Quinn
T M
TM
The Children's Institute for Surgical Science, The Children's Hospital of Philadelphia, and the University of Pennsylvania School of Medicine, 19104, USA.
Sylvester
K G
KG
Kitano
Y
Y
Kitano
Y
Y
Liechty
K W
KW
Jarrett
B P
BP
Adzick
N S
NS
Flake
A W
AW
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*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta