title: miRNA regulated pathways in late stage murine lung development.
abstract: BACKGROUND
  MicroRNAs play important roles in regulating biological processes, including organ morphogenesis and maturation. However, little is known about specific pathways regulated by miRNA during lung development. Between the canalicular and saccular stages of the developing lung several important cellular events occur, including the onset of surfactant synthesis, microvascular remodeling and structural preparation for subsequent alveolarization. The miRNAs that are actively regulated, and the identity of their targets during this important developmental interval in the lung remain elusive.
  
  
  RESULTS
  Using TLDA low density real-time PCR arrays, the expression of 376 miRNAs in male and female fetal mouse lungs of gestational days E15 - E18 were profiled. Statistical analyses identified 25 and 37 miRNAs that changed significantly between sexes and with gestation, respectively. In silico analysis using Ingenuity Pathway Analysis (IPA) identified specific pathways and networks known to be targets of these miRNAs which are important to lung development. Pathways that are targeted by sex regulated miRNAs include retinoin, IGFR1, Tp53 and Akt. Pathways targeted by gestation-regulated miRNAs include VEGFA and mediators of glucose metabolism.
  
  
  CONCLUSIONS
  MiRNAs are differentially regulated across time and between sexes during the canalicular and saccular stages of lung development. Sex-associated differential miRNA expression may regulate the differences in structural and functional male and female lung development, as shown by networks generated using in silico analysis. These data provide a valuable resource to further enhance the understanding of miRNA control of lung development and maturation.
authors.affiliation: Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Sana
authors.initials: S
authors.lastname: Mujahid
authors.forename: Tanya
authors.initials: T
authors.lastname: Logvinenko
authors.forename: Maryann V
authors.initials: MV
authors.lastname: Volpe
authors.forename: Heber C
authors.initials: HC
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008168:Lung / Q000196:embryology*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D038081:Organogenesis; D011247:Pregnancy; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012727:Sex Characteristics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger