Evidence map›Paper›PMID 25876995›Full record

ArticleThe Biochemical journal2015

Erythropoietin-mediated expression of placenta growth factor is regulated via activation of hypoxia-inducible factor-1α and post-transcriptionally by miR-214 in sickle cell disease.

Caryn S Gonsalves, Chen Li, Marthe-Sandrine Eiymo Mwa Mpollo, Vinod Pullarkat, Punam Malik, Stanley M Tahara, Vijay K Kalra

Abstract read
In one paragraph

Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Article
  3. Correlation of changes in circulating levels of hypoxia-induced factor-1α, erythropoietin, and cell-free fetal hemoglobin with feto-maternal pregnancy outcomes.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025
    Article
  4. Review
  5. Review
  6. Hypoxia-inducible factor signaling in pulmonary hypertension.The Journal of clinical investigation · 2020
    Review
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  8. Review
  9. Article
  10. Article
  11. KJournal of hematology & oncology · 2019
    Review
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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

7 authors at 3 institutions in 1 country.

Caryn S GonsalvesDepartments of Biochemistry and Molecular Biology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, U.S.A.
Chen LiDepartments of Biochemistry and Molecular Biology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, U.S.A.
Marthe-Sandrine Eiymo Mwa MpolloDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, U.S.A.
Vinod PullarkatDivision of Hematology, City of Hope, Duarte, CA 91010, U.S.A.
Punam MalikDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, U.S.A.
Stanley M TaharaMolecular Microbiology and Immunology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, U.S.A.
Vijay K KalraDepartments of Biochemistry and Molecular Biology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, U.S.A. vkalra@usc.edu.
University of Southern California · USCincinnati Children's Hospital Medical Center · USCity of Hope · US

Funding

USC RESEARCH CENTER FOR LIVER DISEASES: PILOT PROGRAMSP30DK048522 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KAPLOWITZ, NEIL · 1995 to 2020
$21.8M
PlGF-HIF1a-miRNA Axis in Sickle Pulmonary HypertensionR01HL111372 · NHLBI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI KALRA, VIJAY K., MALIK, PUNAM · 2012 to 2016
$3.1M
NHLBI NIH HHS R01 HL111372NHLBI NIH HHS R01-HL111372NIDDK NIH HHS P30 DK048522NIDDK NIH HHS P30-DK048522
6 · The paper itself

Abstract

Placental growth factor (PlGF) plays an important role in various pathological conditions and diseases such as inflammation, cancer, atherosclerosis and sickle cell disease (SCD). Abnormally high PlGF levels in SCD patients are associated with increased inflammation and pulmonary hypertension (PHT) and reactive airway disease; however, the transcriptional and post-transcriptional mechanisms regulating PlGF expression are not well defined. Herein, we show that treatment of human erythroid cells and colony forming units with erythropoietin (EPO) increased PlGF expression. Our studies showed EPO-mediated activation of HIF-1α led to subsequent binding of HIF-1α to hypoxia response elements (HREs) within the PlGF promoter, as demonstrated by luciferase transcription reporter assays and ChIP analysis of the endogenous gene. Additionally, we showed miR-214 post-transcriptionally regulated the expression of PlGF as demonstrated by luciferase reporter assays using wild-type (wt) and mutant PlGF-3'-UTR constructs. Furthermore, synthesis of miR-214, located in an intron of DNM3 (dynamin 3), was transcriptionally regulated by transcription factors, peroxisome proliferator-activated receptor-α (PPARα) and hypoxia-inducible factor-1α (HIF-1α). These results were corroborated in vivo wherein plasma from SCD patients and lung tissues from sickle mice showed an inverse correlation between PlGF and miR-214 levels. Finally, we observed that miR-214 expression could be induced by fenofibrate, a Food and Drug Administration (FDA) approved PPARα agonist, thus revealing a potential therapeutic approach for reduction in PlGF levels by increasing miR-214 transcription. This strategy has potential clinical implications for several pathological conditions including SCD.

Indexed as

3' Untranslated RegionsAnemia, Sickle CellAnimalsCell LineCells, CulturedCrosses, GeneticErythroid CellsErythroid Precursor CellsErythropoietinGenes, ReporterHematinicsHumansHypoxia-Inducible Factor 1, alpha SubunitLungMiceMice, Inbred C57BL3' Untranslated RegionsErythropoietinHematinicsHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMicroRNAsMIRN214 microRNA, humanPGF protein, humanPgf protein, mousePlacenta Growth FactorPregnancy ProteinsRecombinant Proteinsdynamin 3 opposite strand (DNM3os)fenofibratehypoxia-inducible factor-1α (HIF-1α)microRNA (miRNA)peroxisome proliferator-activated receptor-α (PPARα)placenta growth factor

Identifiers

PMID25876995
PMCPMC4643367
OpenAlexW2330978498

What OpenQuestion holds

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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.