Comparative analyses of lung transcriptomes in patients with alveolar capillary dysplasia with misalignment of pulmonary veins and in Foxf1 heterozygous knockout mice

Partha Sen, Avinash V. Dharmadhikari, Tadeusz Majewski, Mahmoud A. Mohammad, Tanya V. Kalin, Joanna Zabielska, Xiaomeng Ren, Molly Bray, Hannah Brown, Stephen Welty, Sundararajah Thevananther, Claire Langston, Przemyslaw Szafranski, Monica J. Justice, Vladimir V. Kalinichenko, Anna Gambin, John Belmont, Pawel Stankiewicz

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    Abstract

    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.

    Original languageEnglish
    Article numbere94390
    JournalPLoS ONE
    Volume9
    Issue number4
    DOIs
    Publication statusPublished - 10 Apr 2014

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

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