title: Impaired alveolarization and intra-uterine growth restriction in rats: a postnatal genome-wide analysis.
abstract: Intra-uterine growth restriction (IUGR) dramatically increases the risk of bronchopulmonary dysplasia in preterm babies, a disease characterized by arrested alveolarization and abnormal microvascular angiogenesis. We have previously described a rodent low protein diet (LPD) model of IUGR inducing impaired alveolarization, but failed to demonstrate any modification of the classical factors involved in lung development. We performed a genome-wide microarray analysis in 120 rat pups with LPD-induced IUGR and their controls, at three key time points of the alveolarization process: postnatal day 4 (P4): start of alveolarization; P10: peak of the alveolarization process and P21: end of the alveolarization process. Results were analysed using Arraymining, DAVID and KEGG software and validated by qRT-PCR and western blots. Considering a cut-off of 2:1 as significant, 67 transcripts at P4, 102 transcripts at P10 and 451 transcripts at P21 were up-regulated, and 89 transcripts at P4, 25 transcripts at P10 and 585 transcripts at P21 were down-regulated. Automatic functional classification identified three main modified pathways, 'cell adhesion molecules', 'cardiac muscle contraction' and 'peroxisome proliferator-activated receptor' (PPAR). Protein analysis confirmed involvement of the PPAR pathway, with an increase of FABP4, an activator of this pathway, at P4 and an increase of adiponectin at P21. Other data also suggest involvement of the PPAR pathway in impaired alveolarization. Our results show that deregulation of the PPAR pathway may be an important component of the mechanism inducing impaired alveolarization observed in IUGR. The complete dataset is available as GEO profiles on the Gene Expression Omnibus (GEO) database ( www.ncbi.nih.gov/geo/, GEO Accession No. GSE56956).
authors.affiliation: Université Paris Descartes, Paris, France; Fondation PremUp, 53 avenue de l'Observatoire, 75014 Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1141, Paris, France; Assistance Publique - Hôpitaux de Paris, Service de Médecine et Réanimation Néonatales de Port-Royal, Groupe Hospitalier Cochin, Broca, Hôtel-Dieu, 53 Avenue de l'Observatoire, 75014 Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Zana-Taieb
authors.forename: H
authors.initials: H
authors.lastname: Pham
authors.forename: M L
authors.initials: ML
authors.lastname: Franco-Montoya
authors.forename: S
authors.initials: S
authors.lastname: Jacques
authors.forename: F
authors.initials: F
authors.lastname: Letourneur
authors.forename: O
authors.initials: O
authors.lastname: Baud
authors.forename: P H
authors.initials: PH
authors.lastname: Jarreau
authors.forename: D
authors.initials: D
authors.lastname: Vaiman
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000502:physiology; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D015815:Cell Adhesion Molecules / Q000502:physiology; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000503:physiopathology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055106:Genome-Wide Association Study; D006321:Heart / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000254:growth & development* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D047492:Peroxisome Proliferator-Activated Receptors
keywords: alveolarization; bronchopulmonary dysplasia; chronic neonatal lung disease; intra-uterine growth restriction; lung development; microarray analysis; peroxisome proliferator-activated receptor