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Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor.

Publication ,  Journal Article
Fujii, T; Nagamatsu, T; Morita, K; Schust, DJ; Iriyama, T; Komatsu, A; Osuga, Y; Fujii, T
Published in: Sci Rep
September 29, 2017

Placental growth factor (PlGF), abundantly produced from trophoblasts is involved in placental angiogenesis. The regulatory mechanism of its expression is poorly understood. Hypoxia inducible factors (HIFs) are centrally involved in the modulation of cellular function in response to low oxygen conditions. This study aimed to clarify HIF1α and HIF2α expression patterns during cytotrophoblast differentiation into syncytiotrophoblast and the impact of any changes on PlGF expression. HIF proteins were induced remarkably under low oxygen condition (2%). HIF1α expression decreased and HIF2α expression increased when syncytialization of cultured cytotrophoblasts is progressed. Those expression changes of HIF proteins in the process of in-vitro syncytialization was congruent with the immunohistochemical findings in preeclamptic placenta as well as uncomplicated placenta. Low oxygen condition was also associated with reduced PlGF production in syncytializing primary cells and BeWo choriocarcinoma cells. Small interfering RNA-mediated HIF2α knockdown in BeWo cells abrogated hypoxia-associated decreases in PlGF secretion; HIF1α silencing had no significant effect on PlGF secretion. In summary, HIF2α, rather than HIF1α, is most affected by reduced oxygen level during syncytialization and increases in HIF2α trigger a reduction of PlGF production. Our findings suggest new and important connections between HIF proteins and PlGF pathways in the regulation of placental angiogenesis.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

September 29, 2017

Volume

7

Issue

1

Start / End Page

12455

Location

England

Related Subject Headings

  • Trophoblasts
  • Signal Transduction
  • RNA, Small Interfering
  • Primary Cell Culture
  • Pregnancy
  • Pre-Eclampsia
  • Placenta Growth Factor
  • Oxygen
  • Neovascularization, Physiologic
  • Hypoxia-Inducible Factor 1, alpha Subunit
 

Citation

APA
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ICMJE
MLA
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Fujii, T., Nagamatsu, T., Morita, K., Schust, D. J., Iriyama, T., Komatsu, A., & Osuga, Y. (2017). Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor. Sci Rep, 7(1), 12455. https://doi.org/10.1038/s41598-017-12685-w
Fujii, Tatsuya, Takeshi Nagamatsu, Kazuki Morita, Danny J. Schust, Takayuki Iriyama, Atsushi Komatsu, Yutaka Osuga, and Tomoyuki Fujii. “Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor.Sci Rep 7, no. 1 (September 29, 2017): 12455. https://doi.org/10.1038/s41598-017-12685-w.
Fujii T, Nagamatsu T, Morita K, Schust DJ, Iriyama T, Komatsu A, et al. Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor. Sci Rep. 2017 Sep 29;7(1):12455.
Fujii, Tatsuya, et al. “Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor.Sci Rep, vol. 7, no. 1, Sept. 2017, p. 12455. Pubmed, doi:10.1038/s41598-017-12685-w.
Fujii T, Nagamatsu T, Morita K, Schust DJ, Iriyama T, Komatsu A, Osuga Y. Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor. Sci Rep. 2017 Sep 29;7(1):12455.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

September 29, 2017

Volume

7

Issue

1

Start / End Page

12455

Location

England

Related Subject Headings

  • Trophoblasts
  • Signal Transduction
  • RNA, Small Interfering
  • Primary Cell Culture
  • Pregnancy
  • Pre-Eclampsia
  • Placenta Growth Factor
  • Oxygen
  • Neovascularization, Physiologic
  • Hypoxia-Inducible Factor 1, alpha Subunit