title: Inhibition of vascular and epithelial differentiation in murine nitrofen-induced diaphragmatic hernia.
abstract: Neonates with congenital diaphragmatic hernia (DH) die of pulmonary hypoplasia and persistent pulmonary hypertension. We used immunohistochemical localization of alpha-smooth muscle actin (alpha-SMA), platelet endothelial cell adhesion molecule (PECAM)-1, thyroid transcription factor (TTF)-1, surfactant protein (SP) A, SP-C, and competitive RT-PCR quantitation of TTF-1, SP-A, SP-C, and alpha-SMA mRNA expression to characterize the epithelial and vascular phenotype of lungs from ICR fetal mice with a nitrofen-induced DH. Nitrofen (25 mg) was gavage fed to pregnant mice on day 8 of gestation. Fetal mice were delivered on day 17. The diaphragm was examined for a defect, and the lungs were either fixed, sectioned, and immunostained or processed for mRNA isolation. In comparison with control lungs, DH lungs showed increased expression of alpha-SMA mRNA, fewer and more muscular arterioles (alpha-SMA), less well-developed capillary networks (PECAM-1), delayed epithelial development marked by a persistence of TTF-1 in the periphery, and decreased SP-A mRNA and SP-A expression. These data suggest that in the murine nitrofen-induced DH, as in human congenital DH, pulmonary insufficiency is due to an inhibition of peripheral pulmonary development including terminal airway and vascular morphogenesis.
authors.affiliation: Division of Pediatric Surgery, Childrens Hospital Los Angeles Research Institute 90027, USA.
authors.forename: C
authors.initials: C
authors.lastname: Coleman
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Gupta
authors.forename: S
authors.initials: S
authors.lastname: Buckley
authors.forename: J D
authors.initials: JD
authors.lastname: Tefft
authors.forename: C W
authors.initials: CW
authors.lastname: Wuenschell
authors.forename: P
authors.initials: P
authors.lastname: Minoo
authors.forename: K D
authors.initials: KD
authors.lastname: Anderson
authors.forename: D
authors.initials: D
authors.lastname: Warburton
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000502:physiology; D004848:Epithelium / Q000196:embryology / Q000473:pathology; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000196:embryology* / Q000473:pathology; D008168:Lung / Q000098:blood supply* / Q000196:embryology* / Q000473:pathology; D051379:Mice / Q000196:embryology; D008813:Mice, Inbred ICR; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010647:Phenyl Ethers; D011663:Pulmonary Surfactants / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D010647:Phenyl Ethers; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C007350:nitrofen