| First Author | Yang J | Year | 2017 |
| Journal | Cell Biosci | Volume | 7 |
| Pages | 58 | PubMed ID | 29118970 |
| Mgi Jnum | J:254918 | Mgi Id | MGI:6109167 |
| Doi | 10.1186/s13578-017-0186-y | Citation | Yang J, et al. (2017) 14-3-3zeta loss leads to neonatal lethality by microRNA-126 downregulation-mediated developmental defects in lung vasculature. Cell Biosci 7:58 |
| abstractText | 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 14-3-3zeta remain to be determined. In this study, we identified a context specific developmental function of 14-3-3zeta. Results: Targeted deletion of 14-3-3zeta 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 18.5 days post coitum embryos (dpc) showed that 14-3-3zeta-/- 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 14-3-3zeta-/- embryos in the C57Bl/6J background as compared to their wild-type counterparts. Loss of 14-3-3zeta 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 14-3-3zeta 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 14-3-3zeta and downregulation of miR-126 plays a critical role in 14-3-3zeta-loss induced defects in lung vasculature in the C57Bl/6J genetic background. |
