Evidence map›Paper›PMID 19892399›Full record

ArticlePlacenta2009

Hypoxia enhances FGF2- and VEGF-stimulated human placental artery endothelial cell proliferation: roles of MEK1/2/ERK1/2 and PI3K/AKT1 pathways.

K Wang, Y-z Jiang, D-b Chen, J Zheng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Placenta, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Observational
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Expression of G-protein subunit α-14 is increased in human placentas from preeclamptic pregnancies.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2014
    Article
  17. Review
  18. Article
  19. Article
  20. Signaling regulation of fetoplacental angiogenesis.The Journal of endocrinology · 2012
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

K WangDepartment of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, USA.
Y-z Jiang
D-b Chen
J Zheng
University of Wisconsin–Madison · USUniversity of California, Irvine · US

Funding

Unified Cellular and Molecular CoreP01HD038843 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI BIRD, IAN M. · 2001 to 2017
$14.4M
Actions of Estrogen on Uterine Artery EndotheliumR01HL070562 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, DONGBAO · 2001 to 2025
$6.3M
EFFECTS OF NITRIC OXIDE ON FETOPLACENTAL ANGIOGENESISR01HL064703 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI ZHENG, JING · 2000 to 2008
$1.9M
Caveolin-1, Caveolae and Placental AngiogenesisR01HL074947 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, DONGBAO · 2004 to 2007
$1.3M
NHLBI NIH HHS HL64703NHLBI NIH HHS HL70562NHLBI NIH HHS HL74947NHLBI NIH HHS R01 HL064703NHLBI NIH HHS R01 HL070562NHLBI NIH HHS R01 HL074947NICHD NIH HHS HD38843NICHD NIH HHS P01 HD038843
6 · The paper itself

Abstract

Placental development occurs under a low oxygen (2-8% O(2)) environment, which is critical for placental development and angiogenesis. In this study, we examined if hypoxia affected fibroblast growth factor-2 (FGF2)- and vascular endothelial growth factor (VEGF)-stimulated cell proliferation via the mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol-3 kinase (PI3K)/v-akt murine thymomaviral oncogene homologue (AKT1) pathways in human placental artery endothelial (HPAE) cells. We observed that under normoxia (approximately 20% O(2)), FGF2 and VEGF dose-dependently stimulated cell proliferation. Hypoxia (3% O(2)) significantly promoted FGF2- and VEGF-stimulated cell proliferation as compared to normoxia. Under both normoxia and hypoxia, FGF2 rapidly induced ERK1/2 and AKT1 phosphorylation, while VEGF-induced ERK1/2, but not AKT1 phosphorylation. However, hypoxia did not significantly alter FGF2- and VEGF-induced ERK1/2 and AKT1 phosphorylation as compared to normoxia. PD98059 (a MEK1/2 inhibitor) at 20microM and LY294002 (a PI3K inhibitor) at 5microM attenuated FGF2- and VEGF-induced phosphorylation of ERK1/2 and AKT1, respectively. PD98059, even at doses that drastically inhibited FGF2-induced ERK1/2 phosphorylation (20microM) and caused cell loss (40microM), did not affect FGF2-stimulated cell proliferation, which was confirmed by U0126 (another potent MEK1/2 inhibitor). PD98059, however, dose-dependently inhibited VEGF-stimulated cell proliferation. Conversely, LY294002 dose-dependently inhibited FGF2-, but not VEGF-stimulated cell proliferation. These data suggest that in the MEK1/2/ERK1/2 and PI3K/AKT1 pathways differentially mediate FGF2- and VEGF-stimulated HPAE cell proliferation. These results also indicate that hypoxia promotes FGF2- and VEGF-stimulated cell proliferation without further activation of the PI3K/AKT1 and MEK1/2/ERK1/2, respectively.

Indexed as

ArteriesButadienesCell HypoxiaCell ProliferationCells, CulturedChromonesCulture Media, Serum-FreeEndothelial CellsEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesFemaleFibroblast Growth Factor 2FlavonoidsHumansHypoxia-Inducible Factor 1, alpha SubunitMAP Kinase Kinase 12-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-oneAKT1 protein, humanButadienesChromonesCulture Media, Serum-FreeEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesFibroblast Growth Factor 2FlavonoidsHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMAP2K1 protein, humanMAP2K2 protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2MorpholinesNitrilesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktU 0126Vascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID19892399
PMCPMC2788063
OpenAlexW2088011382

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.