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PLoS One. 2014 Apr 10;9(4):e94390. doi: 10.1371/journal.pone.0094390. eCollection 2014.

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

Author information

  • 1Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America.
  • 2Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
  • 3Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
  • 4Division of Pulmonary Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America.
  • 5Institute of Informatics, University of Warsaw, Warsaw, Poland.
  • 6Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
  • 7Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America; Robinson Research Institute, School of Pediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia.
  • 8Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America; Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
  • 9Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America.
  • 10Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
  • 11Institute of Informatics, University of Warsaw, Warsaw, Poland; Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
  • 12Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.

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.

PMID:
24722050
[PubMed - in process]
PMCID:
PMC3983164
Free PMC Article

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