Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor
- Authors
- Jeong, Wooyoung; Bazer, Fuller W.; Song, Gwonhwa; Kim, Jinyoung
- Issue Date
- 8-1월-2016
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- HIF-1; Hypoxia; EGF; Trophectoderm; Cell signaling; Proliferation
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.469, no.2, pp.176 - 182
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 469
- Number
- 2
- Start Page
- 176
- End Page
- 182
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/89817
- DOI
- 10.1016/j.bbrc.2015.11.091
- ISSN
- 0006-291X
- Abstract
- The low oxygen environment in the uterine environment requires pre-implantation embryos to adapt to oxygen deficiency. Hypoxia-inducible actor(HIF)-1 is a master regulator whereby cells adapt to changes in oxygen concentrations. In addition to hypoxic conditions, non-hypoxic stimuli such as growth factors also activate expression of HIF-1. In this study, the mechanisms underlying low oxygen-dependent and epidermal growth factor (EGF)-dependent expression of HIF-1 alpha were explored using porcine trophectoderm (pTr) cells. The results indicated that expression of HIF-1 alpha and HIF-1 beta mRNAs was not affected by low concentrations of oxygen; however, hypoxic conditions markedly increased the abundance of HIF-1 alpha protein, especially in nuclei of pTr cells. Even under normoxic conditions, the abundance of HIF-1 alpha protein increased in response to EGF. This EGF-mediated increase in HIF-1 alpha protein was blocked through inhibition of translation by cycloheximide. The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1 alpha protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. Both hypoxia and EGF induced proliferation of pTr cells. This ability of EGF to stimulate proliferation of pTr cells was suppressed by EGFR siRNA, but not HIF-1 alpha siRNA, but a significant decrease in EGF-induced HIF-1 alpha protein occurred when pTr cells were transfected with HIF-1 alpha siRNA. The results of the present study suggest that pTr cells adapt to oxygen deficiency and proliferate in response to an oxygen-dependent HIF-1 system, and that EGF at maternal conceptus interface can increase the abundance of HIF-1 alpha protein via translational regulation through AKT, ERK1/2 and mTOR signaling cascades. (C) 2015 Elsevier Inc. All rights reserved.
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