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 M. Brown, Stephen Welty, Sundararajah Thevananther, Claire Langston, Przemyslaw Szafranski, Monica J. Justice, Vladimir V. Kalinichenko, Anna Gambin, John Belmont, Pawel Stankiewicz

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 (US)
Article numbere94390
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 10 2014
Externally publishedYes

ASJC Scopus subject areas

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

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