title: Metabolic disturbances of the vitamin A pathway in human diaphragmatic hernia.
abstract: Congenital diaphragmatic hernia (CDH) is a common life-threatening congenital anomaly resulting in high rates of perinatal death and neonatal respiratory distress. Some of the nonisolated forms are related to single-gene mutations or genomic rearrangements, but the genetics of the isolated forms (60% of cases) still remains a challenging issue. Retinoid signaling (RA) is critical for both diaphragm and lung development, and it has been hypothesized that subtle disruptions of this pathway could contribute to isolated CDH etiology. Here we used time series of normal and CDH lungs in humans, in nitrofen-exposed rats, and in surgically induced hernia in rabbits to perform a systematic transcriptional analysis of the RA pathway key components. The results point to CRPBP2, CY26B1, and ALDH1A2 as deregulated RA signaling genes in human CDH. Furthermore, the expression profile comparisons suggest that ALDH1A2 overexpression is not a primary event, but rather a consequence of the CDH-induced lung injury. Taken together, these data show that RA signaling disruption is part of CDH pathogenesis, and also that dysregulation of this pathway should be considered organ specifically.
authors.forename: Karen
authors.initials: K
authors.lastname: Coste
authors.forename: Leonardus W J E
authors.initials: LW
authors.lastname: Beurskens
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanc
authors.forename: Denis
authors.initials: D
authors.lastname: Gallot
authors.forename: Amélie
authors.initials: A
authors.lastname: Delabaere
authors.forename: Loïc
authors.initials: L
authors.lastname: Blanchon
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: André
authors.initials: A
authors.lastname: Labbé
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Rottier
authors.forename: Vincent
authors.initials: V
authors.lastname: Sapin
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D003964:Diaphragm / Q000196:embryology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental; D065630:Hernias, Diaphragmatic, Congenital / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000196:embryology; D008297:Male; D011817:Rabbits; D051381:Rats; D050697:Retinal Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D054840:Retinol-Binding Proteins, Cellular / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014801:Vitamin A / Q000235:genetics / Q000378:metabolism*
chemical_list: D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase