Abstract
Background: The 14-3-3 family of proteins have been reported to play an important role in development in various mouse models, but the context specific developmental functions of 14-3-3η remain to be determined. In this study, we identified a context specific developmental function of 14-3-3η. Results: Targeted deletion of 14-3-3η in the C57Bl/6J murine genetic background led to neonatal lethality due to respiratory distress and could be rescued by out-breeding to the CD-1 or backcrossing to the FVB/NJ congenic background. Histological analysis of lung sections from 18.5days post coitum embryos (dpc) showed that 14-3-3η-/- lung development is arrested at the pseudoglandular stage and exhibits vascular defects. The expression of miR-126, an endothelial-specific miRNA known to regulate lung vascular integrity was down-regulated in the lungs of the 14-3-3η-/- embryos in the C57Bl/6J background as compared to their wild-type counterparts. Loss of 14-3-3η in endothelial cells inhibited the angiogenic capability of the endothelial cells as determined by both trans-well migration assays and tube formation assays and these defects could be rescued by re-expressing miR-126. Mechanistically, loss of 14-3-3η led to reduced Erk1/2 phosphorylation resulting in attenuated binding of the transcription factor Ets2 on the miR-126 promoter which ultimately reduced expression of miR-126. Conclusion: Our data demonstrates that miR-126 is an important angiogenesis regulator that functions downstream of 14-3-3η and downregulation of miR-126 plays a critical role in 14-3-3η-loss induced defects in lung vasculature in the C57Bl/6J genetic background.
Original language | English (US) |
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Article number | 58 |
Journal | Cell and Bioscience |
Volume | 7 |
Issue number | 1 |
DOIs | |
State | Published - Nov 2 2017 |
Keywords
- 14-3-3η
- Angiogenesis
- Lung development
- MiR-126
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
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