Comparative analyses of lung transcriptomes in patients with alveolar capillary dysplasia with misalignment of pulmonary veins and in foxf1 heterozygous knockout mice

• Published in: PloS one 2014-04, Vol.9 (4), p.e94390-e94390
• Main Authors: Sen, Partha, Dharmadhikari, Avinash V, Majewski, Tadeusz, Mohammad, Mahmoud A, Kalin, Tanya V, Zabielska, Joanna, Ren, Xiaomeng, Bray, Molly, Brown, Hannah M, Welty, Stephen, Thevananther, Sundararajah, Langston, Claire, Szafranski, Przemyslaw, Justice, Monica J, Kalinichenko, Vladimir V, Gambin, Anna, Belmont, John, Stankiewicz, Pawel
• Format: Article
• Language: English
• Subjects: Alveoli; Angiogenesis; Animals; Animals, Newborn; Biology; Biology and life sciences; Cancer; Care and treatment; Children & youth; Comparative analysis; Deregulation; Developmental disabilities; Diagnosis; Dysplasia; Esophagus; Etiology; Female; Forkhead Transcription Factors - deficiency; Forkhead Transcription Factors - genetics; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Genes, Lethal; Genetics; Genomes; Haploinsufficiency; Hemorrhage; Heterozygote; Hospitals; Humans; Hypertension; Hypoxia; Infant, Newborn; Informatics; Insulin-like growth factor-binding protein 3; Interleukin 1; Laboratory animals; Lethality; Lung - abnormalities; Lung - blood supply; Lung - metabolism; Lungs; Male; Medicine; Medicine and Health Sciences; Metabolic Networks and Pathways; Mice; Mice, Knockout; Misalignment; Mutation; Neonates; Patients; Pediatrics; Persistent Fetal Circulation Syndrome - genetics; Persistent Fetal Circulation Syndrome - metabolism; Physicians; Pulmonary Alveoli - abnormalities; Pulmonary Alveoli - blood supply; Pulmonary Alveoli - metabolism; Pulmonary arteries; Pulmonary hypertension; Pulmonary Veins - abnormalities; Pulmonary Veins - metabolism; Research and Analysis Methods; Rodents; Studies; Transcription; Transcription factors; Transcriptome; Veins; Veins & arteries
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0094390

Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV) is a developmental disorder of the lungs, primarily affecting their vasculature. FOXF1 haploinsufficiency due to heterozygous genomic deletions and point mutations have been reported in most patients with ACDMPV. The majority of mice with heterozygous loss-of-function of Foxf1 exhibit neonatal lethality with evidence of pulmonary hemorrhage in some of them. By comparing transcriptomes of human ACDMPV lungs with control lungs using expression arrays, we found that several genes and pathways involved in lung development, angiogenesis, and in pulmonary hypertension development, were deregulated. Similar transcriptional changes were found in lungs of the postnatal day 0.5 Foxf1+/- mice when compared to their wildtype littermate controls; 14 genes, COL15A1, COL18A1, COL6A2, ESM1, FSCN1, GRINA, IGFBP3, IL1B, MALL, NOS3, RASL11B, MATN2, PRKCDBP, and SIRPA, were found common to both ACDMPV and Foxf1 heterozygous lungs. Our results advance knowledge toward understanding of the molecular mechanism of ACDMPV, lung development, and its vasculature pathology. These data may also be useful for understanding etiologies of other lung disorders, e.g. pulmonary hypertension, bronchopulmonary dysplasia, or cancer.