Evidence map›Paper›PMID 23383310›Full record

ArticlePloS one2013

PDGF is required for remyelination-promoting IgM stimulation of oligodendrocyte progenitor cell proliferation.

Jens O Watzlawik, Arthur E Warrington, Moses Rodriguez

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.0field-weighted citation impact, top 7% 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

40 citing papers in PubMed, 67 citations in OpenAlex.

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  17. White matter and neurological disorders.Archives of pharmacal research · 2020
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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

3 authors at 1 institution in 1 country.

Jens O WatzlawikDepartments of Neurology and Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America.
Arthur E Warrington
Moses Rodriguez
Mayo Clinic · US

Funding

T cell Function in Murine Model of Multiple SclerosisR01NS032129 · NINDS · MAYO CLINIC ROCHESTER · PI RODRIGUEZ, MOSES · 1994 to 2010
$2.7M
IMMUNE PROMOTION OF REMYELINATIONR01NS024180 · NINDS · MAYO CLINIC ROCHESTER · PI RODRIGUEZ, MOSES · 1987 to 2008
$2.7M
Nanopore Biosensor for Kinetics of Reparative Antibodies on Plasma MembranesR01GM092993 · NIGMS · UNIVERSITY OF MINNESOTA · PI OH, SANG-HYUN · 2010 to 2013
$1.6M
Genetic Analysis of Spontaneous RemyelinationR01NS048357 · NINDS · MAYO CLINIC ROCHESTER · PI BIEBER, ALLAN JAMES · 2008 to 2011
$1.0M
Clinical Translation of a Neuron Protective Recombinant Human AntibodyR21NS073684 · NINDS · MAYO CLINIC ROCHESTER · PI RODRIGUEZ, MOSES · 2011 to 2012
$434k
NIGMS NIH HHS R01 GM092993NINDS NIH HHS R01 NS024180NINDS NIH HHS R01 NS032129NINDS NIH HHS R01 NS048357NINDS NIH HHS R21 NS073684
6 · The paper itself

Abstract

backgroundPromotion of remyelination is a major goal in treating demyelinating diseases such as multiple sclerosis (MS). The recombinant human monoclonal IgM, rHIgM22, targets myelin and oligodendrocytes (OLs) and promotes remyelination in animal models of MS. It is unclear whether rHIgM22-mediated stimulation of lesion repair is due to promotion of oligodendrocyte progenitor cell (OPC) proliferation and survival, OPC differentiation into myelinating OLs or protection of mature OLs. It is also unknown whether astrocytes or microglia play a functional role in IgM-mediated lesion repair.

methodsWe assessed the effect of rHIgM22 on cell proliferation in mixed CNS glial and OPC cultures by tritiated-thymidine uptake and by double-label immunocytochemistry using the proliferation marker, Ki-67. Antibody-mediated signaling events, OPC differentiation and OPC survival were investigated and quantified by Western blots.

resultsrHIgM22 stimulates OPC proliferation in mixed glial cultures but not in purified OPCs. There is no proliferative response in astrocytes or microglia. rHIgM22 activates PDGFαR in OPCs in mixed glial cultures. Blocking PDGFR-kinase inhibits rHIgM22-mediated OPC proliferation in mixed glia. We confirm in isolated OPCs that rHIgM22-mediated anti-apoptotic signaling and inhibition of OPC differentiation requires PDGF and FGF-2. We observed no IgM-mediated effect in mature OLs in the absence of PDGF and FGF-2.

conclusionStimulation of OPC proliferation by rHIgM22 depends on co-stimulatory astrocytic and/or microglial factors. We demonstrate that rHIgM22-mediated activation of PDGFαR is required for stimulation of OPC proliferation. We propose that rHIgM22 lowers the PDGF threshold required for OPC proliferation and protection, which can result in remyelination of CNS lesions.

Indexed as

Analysis of VarianceAnimalsBlotting, WesternBromodeoxyuridineCell ProliferationHumansImmunoglobulin MImmunohistochemistryMicroscopy, FluorescenceMultiple SclerosisMyelin SheathOligodendrogliaPlatelet-Derived Growth FactorRatsRats, Sprague-DawleyStem CellsBromodeoxyuridineImmunoglobulin MPlatelet-Derived Growth FactorThymidine

Identifiers

PMID23383310
PMCPMC3562326
OpenAlexW2069057105

What OpenQuestion holds

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LicenceCC BY
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.