Evidence map›Paper›PMID 28623280›Full record

ArticleScientific reports2017

EV-3, an endogenous human erythropoietin isoform with distinct functional relevance.

Christel Bonnas, Liane Wüstefeld, Daniela Winkler, Romy Kronstein-Wiedemann, Ekrem Dere, Katja Specht, Melanie Boxberg, Torsten Tonn, Hannelore Ehrenreich, Herbert Stadler and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

14 citing papers in PubMed, 24 citations in OpenAlex.

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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

11 authors at 4 institutions in 1 country.

Christel BonnasEpomedics GmbH, Göttingen, Germany. christel.bonnas@epomedics.com.ORCID 0000-0002-5601-516X
Liane WüstefeldClinical Neuroscience, Max Planck Institute of Experimental Medicine and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
Daniela WinklerClinical Neuroscience, Max Planck Institute of Experimental Medicine and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
Romy Kronstein-WiedemannGerman Red Cross Blood Donor Service North-East, Institute of Transfusion Medicine, Dresden, Germany.
Ekrem DereClinical Neuroscience, Max Planck Institute of Experimental Medicine and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
Katja SpechtInstitute of Pathology, Technische Universität München, Munich, Germany.
Melanie BoxbergInstitute of Pathology, Technische Universität München, Munich, Germany.
Torsten TonnGerman Red Cross Blood Donor Service North-East, Institute of Transfusion Medicine, Dresden, Germany.
Hannelore EhrenreichClinical Neuroscience, Max Planck Institute of Experimental Medicine and DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
Herbert StadlerEpomedics GmbH, Göttingen, Germany.
Inge SillaberEpomedics GmbH, Göttingen, Germany.
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 · DEImmunomedics (Germany) · DEGerman Red Cross · DETechnical University of Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Generation of multiple mRNAs by alternative splicing is well known in the group of cytokines and has recently been reported for the human erythropoietin (EPO) gene. Here, we focus on the alternatively spliced EPO transcript characterized by deletion of exon 3 (hEPOΔ3). We show co-regulation of EPO and hEPOΔ3 in human diseased tissue. The expression of hEPOΔ3 in various human samples was low under normal conditions, and distinctly increased in pathological states. Concomitant up-regulation of hEPOΔ3 and EPO in response to hypoxic conditions was also observed in HepG2 cell cultures. Using LC-ESI-MS/MS, we provide first evidence for the existence of hEPOΔ3 derived protein EV-3 in human serum from healthy donors. Contrary to EPO, recombinant EV-3 did not promote early erythroid progenitors in cultures of human CD34+ haematopoietic stem cells. Repeated intraperitoneal administration of EV-3 in mice did not affect the haematocrit. Similar to EPO, EV-3 acted anti-apoptotic in rat hippocampal neurons exposed to oxygen-glucose deprivation. Employing the touch-screen paradigm of long-term visual discrimination learning, we obtained first in vivo evidence of beneficial effects of EV-3 on cognition. This is the first report on the presence of a naturally occurring EPO protein isoform in human serum sharing non-erythropoietic functions with EPO.

Indexed as

Amino Acid SequenceCell Line, TumorColony-Forming Units AssayErythropoietinGene Expression RegulationHematopoietic Stem CellsHumansHypoxiaImmunoprecipitationMaleModels, MolecularProtein ConformationProtein IsoformsPyramidal CellsRecombinant ProteinsRNA SplicingEPO protein, humanErythropoietinProtein IsoformsRecombinant Proteins

Identifiers

PMID28623280
PMCPMC5473850
OpenAlexW2626761667

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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.