O-GlcNAc cycling enzymes control vascular development of the placenta by modulating the levels of HIF-1 alpha
SCIE
SCOPUS
- Title
- O-GlcNAc cycling enzymes control vascular development of the placenta by modulating the levels of HIF-1 alpha
- Authors
- Yang, YR; Jang, HJ; Lee, YH; Kim, IS; Lee, H; Ryu, SH; Suh, PG
- Date Issued
- 2015-10
- Publisher
- W B SAUNDERS CO LTD
- Abstract
- Introduction: Placental vasculogenesis is essential for fetal growth and development, and is affected profoundly by oxygen tension (hypoxia). Hypoxia-inducible factor-1 alpha: (HIF-1 alpha), which is stabilized at the protein level in response to hypoxia, is essential for vascular morphogenesis in the placenta. Many studies suggested that responses to hypoxia is influenced by O-GlcNAcylation. O-GlcNAcylation is regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that catalyze the addition and removal of O-GlcNAc respectively. Methods: We generated OGA deficient mice and evaluated OGA(-/-) placentas. The analysis of OGA(-/-) placentas was focused on morphological change and placental vasculogenesis. HIF-1 alpha: protein stability or transcriptional activity under dysregulation of O-GlcNAcylation were evaluated by Western blot, RT-qPCR and luciferase reporter gene assays in MEFs or MS1 cell line. Results: Deletion of OGA results in defective placental vasculogenesis. OGA(-/-) placentas showed an abnormal placental shape and reduced vasculature in the labyrinth, which caused a developmental delay in the embryos. OGA deletion, which elevates O-GlcNAcylation and downregulates O-GlcNAc transferase (OGT), suppressed HIF-1 alpha stabilization and the transcription of its target genes. In contrast, the overexpression of O-GlcNAc cycling enzymes enhanced the expression and transcriptional activity of HIF-1 alpha. Discussion: These results suggest that OGA plays a critical role in placental vasculogenesis by modulating HIP-1 alpha stabilization. Control of O-GlcNAcylation is essential for placental development. (C) 2015 Elsevier Ltd. All rights reserved.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/35452
- DOI
- 10.1016/J.PLACENTA.2015.08.001
- ISSN
- 0143-4004
- Article Type
- Article
- Citation
- PLACENTA, vol. 36, no. 10, page. 1063 - 1068, 2015-10
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.