Expression of surfactant proteins and thyroid transcription factor 1 in an ovine model of congenital diaphragmatic hernia.
OBJECTIVE
The question of delayed lung maturation in congenital diaphragmatic hernia (CDH) is pending. Data about surfactant proteins (SPs) are sparse in human fetuses and discrepant in the ovine CDH model. The purpose of this study was to investigate, in the ovine surgically created CDH model, the expression of SPs and of thyroid transcription factor 1 (TTF-1), a key regulator of lung development that also controls the expression of surfactant proteins.


METHODS
Diaphragmatic hernia (DH) was created surgically in lamb fetuses on day 85 of gestation. On day 139, 5 DH and 6 control fetuses were retrieved by cesarean section. The mRNA levels for SPs and TTF-1 were determined by Northern blot analysis; SP-A and SP-B protein levels were assessed by Western blot analysis.


RESULTS
In DH lungs, SP-A, SP-B, and SP-C messenger RNAs were diminished by 82%, 67%, and 32%, respectively, compared with control level. SP-A and SP-B protein amounts were decreased consistently. TTF-1 expression was not altered in the surgical model.


CONCLUSIONS
SP's deficiency appears to be a common feature of the various CDH models. By contrast with the nitrofen model, TTF-1 expression was not altered in the surgical model indicating different underlying molecular mechanisms in both models.
Benachi
Alexandra
A
Maternité Hospitalo-Universitaire Necker-Enfants Malades, Paris, France.
Chailley-Heu
Bernadette
B
Barlier-Mur
Anne-Marie
AM
Dumez
Yves
Y
Bourbon
Jacques
J
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005325:Fetal Organ Maturity; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006548:Hernia, Diaphragmatic / Q000196:embryology / Q000378:metabolism; D065630:Hernias, Diaphragmatic, Congenital; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000196:embryology*; D009687:Nuclear Proteins / Q000378:metabolism*; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012756:Sheep; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000378:metabolism*
D018398:Homeodomain Proteins; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors