Altered insulin-like growth factor I mRNA expression in human hypoplastic lung in congenital diaphragmatic hernia.
OBJECTIVE
Insulin-like growth factor I (IGF-I) is a peptide growth factor that is synthesized in many organs during human development and plays a role in the growth and differentiation of tissue. IGF-I has been shown to be produced in rat and human fetal lung and to be an important mitogen involved in lung growth and development. The cells responsible for the synthesis of IGF-I in lung in vivo have been demonstrated to be type II pneumocytes, alveolar macrophages, and mesenchymal cells. Recent studies have shown that IGF-I mRNA expression in the lung is predominant during fetal life and decreases before birth, becoming barely detectable in the neonatal lung. The aim of this study was to investigate IGF-I mRNA expression in CDH lung to understand the basis of pulmonary hypoplasia in newborns with CDH.


METHODS
Lung tissue samples were obtained during autopsy from 13 patients with CDH. Nine were full-term newborns (mean age, 3.8 days), and four were stillborns. Normal lung tissue from eight sudden infant death syndrome infants (mean age, 15.3 days) acted as controls. In situ hybridization was performed on frozen sections using IGF-I-specific and digoxigenin-labeled oligonucleotide probe and visualized by nitro blue tetrazolium staining.


RESULTS
In control lung, IGF-I mRNA expression was absent or weak in type II pneumocytes and alveolar macrophages. In contrast, there was strong IGF-I mRNA expression in type II pneumocytes and alveolar macrophages in hypoplastic CDH lung in newborns as well as stillborns.


CONCLUSIONS
The findings of strong IGF-I mRNA expression in the hypoplastic lung suggest that lung hypoplasia in CDH is a persistence of fetal stage of lung development.
Miyazaki
E
E
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Ohshiro
K
K
Taira
Y
Y
Puri
P
P
D006548:Hernia, Diaphragmatic / Q000378:metabolism* / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I