Evidence for decreased lipofibroblast expression in hypoplastic rat lungs with congenital diaphragmatic hernia.

[congenital diaphragmatic hernia]

Pulmonary hypoplasia (PH ) is a serious condition in newborns with congenital diaphragmatic hernia (CDH ). Lipid-containing interstitial fibroblasts (LIFs ) play an essential role in fetal lung maturation by stimulating alveolarization and lipid homeostasis . In rodents , LIFs are first evident during the canalicular phase of lung development with a significant increase over the last 4 Â days of gestation . Adipocyte differentiation-related protein (ADRP ), a functional lipogenic molecular marker characterizing LIFs , is highly expressed in fetal lungs during this critical time period . We hypothesized that LIF expression in hypoplastic rat lungs is decreased in the nitrofen-induced CDH model , which is accompanied by reduced alveolar ADRP expression and lipid content .On embryonic day 9 .5 (E 9 .5 ), time-mated rats received either nitrofen or vehicle . Fetuses were sacrificed on selected time points E 18 .5 and E 21 .5 , and dissected lungs were divided into controls and CDH -associated PH . Pulmonary gene expression levels of ADRP were determined by quantitative real-time polymerase chain reaction . ADRP immunohistochemistry and oil red O staining were used to assess pulmonary protein expression and lipid content . Immunofluorescence double staining for alpha smooth muscle actin , which is known to be absent in LIFs , and lipid droplets was performed to evaluate the pulmonary expression of this specific subset of fibroblasts .Relative mRNA expression of ADRP was significantly reduced in lungs of CDH -associated PH on E 18 .5 and E 21 .5 compared to controls . ADRP immunoreactivity and lipid staining were markedly diminished in alveolar mesenchymal cells of CDH -associated PH on E 18 .5 and E 21 .5 compared to controls . Confocal laser scanning microscopy demonstrated markedly decreased LIF expression in alveolar interstitium of CDH -associated PH on E 18 .5 and E 21 .5 compared to controls .Decreased pulmonary LIF expression during late gestation suggests impaired LIF functioning in the nitrofen-induced CDH model , which may cause disruption in fetal alveolarization and lipid homeostasis , and thus contribute to the development of PH .

Diseases
Validation

Diseases presenting "congenital diaphragmatic hernia" symptom

congenital diaphragmatic hernia

megacystis-microcolon-intestinal hypoperistalsis syndrome

This symptom has already been validated