Administration of antenatal glucocorticoids upregulates peptide growth factor gene expression in nitrofen-induced congenital diaphragmatic hernia in rats.
OBJECTIVE
There is increasing evidence to suggest that various growth factors play a crucial role in fetal lung growth and morphogenesis. An array of peptide growth factors regulate cell proliferation, differentiation, and various other cell functions in the developing lung. The aim of this study was to investigate the effect of antenatal glucocorticoids administration on gene expression of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta1 in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats.


METHODS
A CDH model was induced in pregnant rats after administration of nitrofen. Dexamethasone (Dex; 0.25 mg/kg) was given intraperitoneally on day 18.5 and 19.5 of gestation (term, day 22). Cesarean section was performed on day 21 of gestation. mRNA was extracted from left lung and reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate mRNA expression of each growth factors. Relative levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin, a housekeeping gene known to be expressed at a constant level.


RESULTS
Relative mRNA levels of bFGF and TGF-beta1 were decreased significantly in CDH lung compared with controls. Antenatal Dex treatment up-regulated gene expression of bFGF, PDGF, and TGF-beta1 in the hypoplastic CDH lung.


CONCLUSIONS
The authors' findings suggest that decreased gene expression of bFGF, PDGF, and TGF-beta1 in the CDH lung may suppress lung growth and development. Increased gene expression of bFGF, PDGF, and TGF-beta1 in Dex-treated lung suggests that antenatal glucocorticoid administration may accelerate fetal lung growth by up-regulating these growth factors.
Oue
T
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Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Shima
H
H
Taira
Y
Y
Puri
P
P
D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005938:Glucocorticoids / Q000008:administration & dosage*; D006133:Growth Substances / Q000378:metabolism*; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000196:embryology* / Q000378:metabolism; D008168:Lung / Q000196:embryology / Q000378:metabolism; D010647:Phenyl Ethers; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D005938:Glucocorticoids; D006133:Growth Substances; D010647:Phenyl Ethers; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D003907:Dexamethasone; C007350:nitrofen