Evidence map›Paper›PMID 27175488›Full record

ArticlePloS one2016

Neuregulin-1 Administration Protocols Sufficient for Stimulating Cardiac Regeneration in Young Mice Do Not Induce Somatic, Organ, or Neoplastic Growth.

Balakrishnan Ganapathy, Nikitha Nandhagopal, Brian D Polizzotti, David Bennett, Alparslan Asan, Yijen Wu, Bernhard Kühn

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Adult Cardiomyocyte Proliferation: a New Insight for Myocardial Infarction Therapy.Journal of cardiovascular translational research · 2021
    Review
  5. Article
  6. Review
  7. Transcriptional Programs and Regeneration Enhancers Underlying Heart Regeneration.Journal of cardiovascular development and disease · 2018
    Review
  8. Article
  9. Review
  10. Article
  11. 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

7 authors at 4 institutions in 1 country.

Balakrishnan GanapathyDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, United States of America.
Nikitha NandhagopalDepartment of Pediatrics, University of Pittsburgh, and Richard King Mellon Institute for Pediatric Research and Division of Pediatric Cardiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, United States of America.
Brian D PolizzottiDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, United States of America.
David BennettPre-clinical MRI Core, Beth Israel Deaconess Medical Center, Boston, MA 02115, United States of America.
Alparslan AsanDepartment of Pediatrics, University of Pittsburgh, and Richard King Mellon Institute for Pediatric Research and Division of Pediatric Cardiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, United States of America.
Yijen WuDepartment of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15224, United States of America.
Bernhard KühnDepartment of Cardiology, Boston Children's Hospital, Boston, MA 02115, United States of America.
University of Pittsburgh · USBeth Israel Deaconess Medical Center · USHarvard University · USRichard King Mellon Foundation · US

Funding

RESEARCH METHODS IN PEDIATRICS HEART DISEASET32HL007572 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI Sarah D DE FERRANTI, Jane W. Newburger · 1985 to 2026
$13.0M
BIDMC 9.4T 20cm Biospec MRI SystemS10RR028792 · NCRR · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BURSTEIN, DEBORAH · 2009 to 2009
$2.4M
Myofibril disassembly during neonatal heart muscle cell proliferationR01HL106302 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KUHN, BERNHARD · 2011 to 2015
$2.1M
Periostin in Myocardial Injury and RegenerationK08HL085143 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI KUHN, BERNHARD · 2009 to 2013
$645k
NCRR NIH HHS S10 RR028792NHLBI NIH HHS K08 HL085143NHLBI NIH HHS R01 HL106302NHLBI NIH HHS T32 HL007572
6 · The paper itself

Abstract

backgroundWe previously developed and validated a strategy for stimulating heart regeneration by administration of recombinant neuregulin (rNRG1), a growth factor, in mice. rNRG1 stimulated proliferation of heart muscle cells, cardiomyocytes, and was most effective when administration began during the neonatal period. Our results suggested the use of rNRG1 to treat pediatric patients with heart failure. However, administration in this age group may stimulate growth outside of the heart.

methodsNRG1 and ErbB receptor expression was determined by RT-PCR. rNRG1 concentrations in serum were quantified by ELISA. Mice that received protocols of recombinant neuregulin1-β1 administration (rNRG1, 100 ng/g body weight, daily subcutaneous injection for the first month of life), previously shown to induce cardiac regeneration, were examined at pre-determined intervals. Somatic growth was quantified by weighing. Organ growth was quantified by MRI and by weighing. Neoplastic growth was examined by MRI, visual inspection, and histopathological analyses. Phospho-ERK1/2 and S6 kinase were analyzed with Western blot and ELISA, respectively.

resultsLung, spleen, liver, kidney, brain, and breast gland exhibited variable expression of the NRG1 receptors ErbB2, ErbB3, ErbB4, and NRG1. Body weight and tibia length were not altered in mice receiving rNRG1. MRI showed that administration of rNRG1 did not alter the volume of the lungs, liver, kidneys, brain, or spinal cord. Administration of rNRG1 did not alter the weight of the lungs, spleen, liver, kidneys, or brain. MRI, visual inspection, and histopathological analyses showed no neoplastic growth. Follow-up for 6 months showed no alteration of somatic or organ growth. rNRG1 treatment increased the levels of phospho-ERK1/2, but not phospho-S6 kinase.

conclusionsAdministration protocols of rNRG1 for stimulating cardiac regeneration in mice during the first month of life did not induce unwanted growth effects. Further studies may be required to determine whether this is the case in a corresponding human population.

Indexed as

AgingAnimalsAnimals, NewbornErbB ReceptorsExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHeartHumansKidneyMiceMorphogenesisNeoplasmsNeuregulin-1Organ SizePhosphorylationRecombinant ProteinsErbB ReceptorsExtracellular Signal-Regulated MAP KinasesNeuregulin-1Recombinant ProteinsRibosomal Protein S6 Kinases

Identifiers

PMID27175488
PMCPMC4866786
OpenAlexW2351904894

What OpenQuestion holds

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LicenceCC BY
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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.