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Cited by 310

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

Cytotrophoblasts Up-Regulate Soluble Fms-Like Tyrosine Kinase-1 Expression under Reduced Oxygen: An Implication for the Placental Vascular Development and the Pathophysiology of Preeclampsia

Open access
Nagamatsu, Takeshi, Fujii, Tomoyuki, Kusumi, Maki, Zou, Li, Yamashita, Takahiro, Osuga, Yutaka, Momoeda, Mikio, Kozuma, Shirou, Taketani, Yuji·2004·Endocrinology
DOI 10.1210/en.2004-0533
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Abstract

Sufficient cytotrophoblast (CT) invasion into the uterine wall and subsequent remodeling of maternal uterine vasculature is critical to establish uteroplacental circulation. The production of vascular endothelial growth factor (VEGF) family molecules is confirmed in placental cells including CTs, but it is not elucidated how the VEGF system in CTs is controlled by oxygen tension and how it is involved in the development of placental circulation. To address this, we explored the effect of oxygen tension on the expression of VEGF, placenta growth factor (PlGF), and their antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1) using ELISA and real-time PCR in a primary CT cell culture. For comparison, the same was conducted in parallel using other cells comprising placenta, such as human umbilical vein endothelial cells (HUVECs) and villous fibroblasts (VFs). Reduced oxygen resulted in a pronounced increase in sFlt-1 mRNA amount and sFlt-1 release into the culture media in CTs, whereas this was not the case with HUVECs and VFs. Free (not bound to sFlt-1) VEGF was not detected in CT culture media regardless of oxygen concentration, even though VEGF expression was stimulated by reduced oxygen in CTs, which was similar to the stimulation in HUVECs and VFs. Free PlGF was also diminished in CT culture media by reduced oxygen. These results implicate that CTs possess a unique property to enhance sFlt-1 production under reduced oxygen, which could consequently antagonize angiogenic activity of VEGF and PlGF. The presented findings might provide a framework with which to understand the mechanism of uterine vascular remodeling and its perturbations as exemplified in preeclampsia.

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Metadata

Authors
Nagamatsu, T., Fujii, T., Kusumi, M., Zou, L., Yamashita, T., Osuga, Y., Momoeda, M., Kozuma, S., & Taketani, Y.
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2004-11-01
Volume
145
Issue
11
Pages
4838-4845
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2004-0533
OpenAlex
W2014894250
Cited by
310
References
34
FWCI
15.07
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Cytotrophoblasts Up-Regulate Soluble Fms-Like Tyrosine Kinase-1 Expression under Reduced Oxygen: An Implication for the Placental Vascular Development and the Pathophysiology of Preeclampsia. https://app.cochat.ai/papers/10.1210/en.2004-0533
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Nagamatsu, T., Fujii, T., Kusumi, M., Zou, L., Yamashita, T., Osuga, Y., Momoeda, M., Kozuma, S., & Taketani, Y. (2004). Cytotrophoblasts Up-Regulate Soluble Fms-Like Tyrosine Kinase-1 Expression under Reduced Oxygen: An Implication for the Placental Vascular Development and the Pathophysiology of Preeclampsia. Endocrinology. https://doi.org/10.1210/en.2004-0533

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