Evidence map›Paper›PMID 25550463›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

The hypoxia-inducible miR-429 regulates hypoxia-inducible factor-1α expression in human endothelial cells through a negative feedback loop.

Sylwia Bartoszewska, Kinga Kochan, Arkadiusz Piotrowski, Wojciech Kamysz, Renata J Ochocka, James F Collawn, Rafal Bartoszewski

Open access · greenAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

81 citing papers in PubMed, 150 citations in OpenAlex.

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21 more citing papers are in PubMed but not listed here.

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 2 institutions in 2 countries.

Sylwia BartoszewskaDepartments of *Inorganic Chemistry and Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland; and Department of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, Birmingham, Alabama, USA.
Kinga KochanDepartments of *Inorganic Chemistry and Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland; and Department of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, Birmingham, Alabama, USA.
Arkadiusz PiotrowskiDepartments of *Inorganic Chemistry and Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland; and Department of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, Birmingham, Alabama, USA.
Wojciech KamyszDepartments of *Inorganic Chemistry and Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland; and Department of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, Birmingham, Alabama, USA.
Renata J OchockaDepartments of *Inorganic Chemistry and Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland; and Department of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, Birmingham, Alabama, USA.
James F CollawnDepartments of *Inorganic Chemistry and Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland; and Department of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, Birmingham, Alabama, USA jcollawn@uab.edu rafalbar@gumed.edu.pl.
Rafal BartoszewskiDepartments of *Inorganic Chemistry and Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland; and Department of Cell, Developmental and Integrative Biology, University of Alabama, Birmingham, Birmingham, Alabama, USA jcollawn@uab.edu rafalbar@gumed.edu.pl.
Gdańsk Medical University · PLUniversity of Alabama at Birmingham · US

Funding

Cell Biology of CFTR in Polarized EpitheliaR01DK060065 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI COLLAWN, JAMES F. · 2003 to 2013
$3.1M
NIDDK NIH HHS 5R01DK060065NIDDK NIH HHS R01 DK060065
6 · The paper itself

Abstract

Hypoxia-inducible factors (HIFs) 1 and 2 are dimeric α/β transcription factors that regulate cellular responses to low oxygen. HIF-1 is induced first, whereas HIF-2 is associated with chronic hypoxia. To determine how HIF1A mRNA, the inducible subunit of HIF-1, is regulated during hypoxia, we followed HIF1A mRNA levels in primary HUVECs over 24 hours using quantitative PCR. HIF1A and VEGF A (VEGFA) mRNA, a transcriptional target of HIF-1, increased ∼ 2.5- and 8-fold at 2-4 hours, respectively. To determine how the mRNAs were regulated, we identified a microRNA (miRNA), miR-429, that destabilized HIF1A message and decreased VEGFA mRNA by inhibiting HIF1A. Target protector analysis, which interferes with miRNA-mRNA complex formation, confirmed that miR-429 targeted HIF1A message. Desferoxamine treatment, which inhibits the hydroxylases that promote HIF-1α protein degradation, stabilized HIF-1 activity during normoxic conditions and elevated miR-429 levels, demonstrating that HIF-1 promotes miR-429 expression. RNA-sequencing-based transcriptome analysis indicated that inhibition of miRNA-429 in HUVECs up-regulated 209 mRNAs, a number of which regulate angiogenesis. The results demonstrate that HIF-1 is in a negative regulatory loop with miR-429, that miR-429 attenuates HIF-1 activity by decreasing HIF1A message during the early stages of hypoxia before HIF-2 is activated, and this regulatory network helps explain the HIF-1 transition to HIF-2 during chronic hypoxia in endothelial cells.

Indexed as

Basic Helix-Loop-Helix ProteinsCell HypoxiaEndothelial PAS Domain-Containing Protein 1Feedback, PhysiologicalHumansHuman Umbilical Vein Endothelial CellsHypoxia-Inducible Factor 1, alpha SubunitHypoxia-Inducible Factor-Proline DioxygenasesMicroRNAsMixed Function OxygenasesModels, BiologicalNeovascularization, PhysiologicProteolysisRepressor ProteinsRNA, MessengerRNA StabilityBasic Helix-Loop-Helix ProteinsEGLN1 protein, humanEndothelial PAS Domain-Containing Protein 1HIF1AN protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitHypoxia-Inducible Factor-Proline DioxygenasesMicroRNAsMIRN429 microRNA, humanMixed Function OxygenasesRepressor ProteinsRNA, MessengerVascular Endothelial Growth Factor AVEGFA protein, humanangiogenesisHIF-2hypoxamiRmiRNAVEGF A

Identifiers

PMID25550463
PMCPMC4396612
OpenAlexW2005574452

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.