RT Journal Article
SR Electronic
T1 Downregulated BMPR2 signaling pathway in nitrofen-induced pulmonary hypoplasia
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p4306
VO 38
IS Suppl 55
A1 Martine Makanga
A1 Celine Dewachter
A1 Benoit Rondelet
A1 Robert Naeije
A1 Laurence Dewachter
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p4306.abstract
AB Background: Despite remarkable progress in resuscitation and intensive care, morbidity and mortality in congenital diaphragmatic hernia (CDH) remain high due to severe pulmonary hypoplasia. However, pathogenesis associated with CDH is still not clearly understood. The bone morphogenetic protein receptor (BMPR) type 2 signaling pathway plays a crucial role in fetal lung development.Hypothesis: We sought to determine whether BMPR2 signaling pathway is altered in the nitrofen-induced pulmonary hypoplasia associated to CDH.Methods: Pregnant rats were exposed to either 100 mg nitrofen or olive oil on day 9 (D9) of gestation. At D17 and D19, embryos were delivered by cesarean and sacrificed to check if diaphragmatic hernia existed. Fetal lung, heart and liver tissue weights and body weight of each fetus were recorded. Lung tissue was harvested for pathobiological evaluation (by immunohistochemistry and RTQPCR).Results: Lung, heart and liver weight-to-body weight ratios decreased by 20, 30 and 25% (p<0.05) at D17 and by 25, 15 and 25% (p<0.05) at D21. In the CDH group, at D21, the airway septa were thicker and the radial alveolar count was significantly lower compared to controls. In the lungs, gene expression of BMPR2 was decreased in the nitrofen group at D17 and D21, together with decreased gene expression of the DNA binding protein 1 (Id1), the major target of the BMP signaling pathway. At D17 (but not at D21), pulmonary gene expression of gremlin, a BMPR antagonist, was increased, while pulmonary gene expression of BMP4, a BMPR agonist, decreased.Conclusions: In nitrofen-induced CDH, BMPR2 signaling pathway is downregulated in hypoplastic lungs at both early and late stages of lung development.