Evidence map›Paper›PMID 26028220›Full record

ArticleDevelopmental cell2015

HIF1α Represses Cell Stress Pathways to Allow Proliferation of Hypoxic Fetal Cardiomyocytes.

Nuno Guimarães-Camboa, Jennifer Stowe, Ivy Aneas, Noboru Sakabe, Paola Cattaneo, Lindsay Henderson, Michael S Kilberg, Randall S Johnson, Ju Chen, Andrew D McCulloch and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Developmental cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.

0numbers the graph read from it
0cells of the map it votes in
100citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

100 citing papers in PubMed, 152 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Endometrial Epithelial Lactate Deficiency Drives CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  6. Review
  7. Review
  8. Metabolic changes during cardiac regeneration in the axolotl.Developmental dynamics : an official publication of the American Association of Anatomists · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
    Review
  20. Review

40 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

13 authors at 6 institutions in 3 countries.

Nuno Guimarães-CamboaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Biomedical Sciences Abel Salazar and GABBA Graduate Program, University of Porto, Porto 4050-313, Portugal.
Jennifer StoweDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Ivy AneasDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Noboru SakabeDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Paola CattaneoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Lindsay HendersonDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA.
Michael S KilbergDepartment of Biochemistry and Molecular Biology, Shands Cancer Center and Center for Nutritional Sciences, University of Florida College of Medicine, Gainesville, FL 32160, USA.
Randall S JohnsonDepartment of Physiology, Development and Neuroscience, University of Cambridge, CB2 3EG Cambridge, UK.
Ju ChenDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Andrew D McCullochDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Marcelo A NobregaDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Sylvia M EvansSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: syevans@ucsd.edu.
Alexander C ZambonDepartment of Biopharmaceutical Sciences, Keck Graduate Institute, Claremont, CA 91711, USA. Electronic address: azambon@kgi.edu.
University of California San Diego · USUniversity of Chicago · USKeck Graduate Institute · USUniversidade do Porto · PTUniversity of Cambridge · GBUniversity of Florida Health · US

Funding

UCSD/SDSU IRACDAK12GM068524 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TREJO, JOANN · 2003 to 2025
$24.4M
Systems Biology CoreP01HL098053 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI POWELL, FRANK L. · 2010 to 2014
$10.2M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
The Role of Cypher and ENH in heartR01HL066100 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, JU · 2002 to 2015
$5.3M
Approaches to Cardiac RegenerationDP1OD006428 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EVANS, SYLVIA M · 2009 to 2011
$2.3M
Endocardial Pathways Regulated by Tbx20R01HL119967 · NHLBI · UNIVERSITY OF CHICAGO · PI EVANS, SYLVIA M, NOBREGA, MARCELO A. · 2014 to 2017
$2.2M
Nesprin 1 and 2 in cardiac structure, function, and diseaseR01HL106968 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, JU · 2011 to 2015
$1.9M
Approaches to Cardiac RegenerationDP1HL117649 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EVANS, SYLVIA M · 2012 to 2013
$1.5M
Temporal and Spatial BMP Signalling and CardiogenesisR01HL066276 · NHLBI · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI EVANS, SYLVIA M · 2001 to 2004
$1.4M
Amino Acid Regulation of Alternative SplicingR01DK092062 · NIDDK · UNIVERSITY OF FLORIDA · PI KILBERG, MICHAEL S. · 2011 to 2014
$1.3M
Amino Acid Regulation of the Fos/Jun Transcription FactorsR01DK094729 · NIDDK · UNIVERSITY OF FLORIDA · PI KILBERG, MICHAEL S. · 2011 to 2014
$1.2M
NHLBI NIH HHS DP1 HL117649NHLBI NIH HHS HL117649NHLBI NIH HHS HL119967NHLBI NIH HHS P01 HL098053NHLBI NIH HHS P01 HL098053-04NHLBI NIH HHS R01 HL066100NHLBI NIH HHS R01 HL066276NHLBI NIH HHS R01 HL106968NHLBI NIH HHS R01HL106968NHLBI NIH HHS R01 HL119967NHLBI NIH HHS R01HL66100NIDDK NIH HHS DK092062NIDDK NIH HHS DK094729NIDDK NIH HHS R01 DK092062NIDDK NIH HHS R01 DK094729NIGMS NIH HHS GM068524NIH HHS DP1 OD006428NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Transcriptional mediators of cell stress pathways, including HIF1α, ATF4, and p53, are key to normal development and play critical roles in disease, including ischemia and cancer. Despite their importance, mechanisms by which pathways mediated by these transcription factors interact with one another are not fully understood. In addressing the controversial role of HIF1α in cardiomyocytes (CMs) during heart development, we discovered a mid-gestational requirement for HIF1α for proliferation of hypoxic CMs, involving metabolic switching and a complex interplay among HIF1α, ATF4, and p53. Loss of HIF1α resulted in activation of ATF4 and p53, the latter inhibiting CM proliferation. Bioinformatic and biochemical analyses revealed unexpected mechanisms by which HIF1α intersects with ATF4 and p53 pathways. Our results highlight previously undescribed roles of HIF1α and interactions among major cell stress pathways that could be targeted to enhance proliferation of CMs in ischemia and may have relevance to other diseases, including cancer.

Indexed as

Cell ProliferationActivating Transcription Factor 4AnimalsBiomarkersBlotting, WesternCells, CulturedEmbryo, MammalianFemaleFetusFlow CytometryFluorescent Antibody TechniqueGene Expression ProfilingHypoxiaHypoxia-Inducible Factor 1, alpha SubunitImmunoenzyme TechniquesMaleActivating Transcription Factor 4Atf4 protein, mouseBiomarkersHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitRNA, MessengerTumor Suppressor Protein p53

Identifiers

PMID26028220
PMCPMC4509618
OpenAlexW1523978214

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.