Evidence map›Paper›PMID 20645409›Full record

ArticleGlia2010

Human remyelination promoting antibody inhibits apoptotic signaling and differentiation through Lyn kinase in primary rat oligodendrocytes.

J Watzlawik, E Holicky, D D Edberg, D L Marks, A E Warrington, B R Wright, R E Pagano, M Rodriguez

Open access · greenAbstract read
In one paragraph

Article in Glia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

30 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
  2. Article
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  5. Article
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  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Remyelinating Pharmacotherapies in Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Review
  13. Review
  14. Review
  15. Concomitant Use of Neuroprotective Drugs in Neuro Rehabilitation of Multiple Sclerosis.International journal of physical medicine & rehabilitation · 2016
    Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. 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

8 authors at 1 institution in 1 country.

J WatzlawikDepartment of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
E Holicky
D D Edberg
D L Marks
A E Warrington
B R Wright
R E Pagano
M Rodriguez
Mayo Clinic · US

Funding

INTRACELLULAR TRANSLOCATION AND METABOLISM OF LIPIDSR01GM022942 · NIGMS · MAYO CLINIC ROCHESTER · PI MARKS, DAVID LARRY · 1985 to 2010
$5.3M
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
NIAID NIH HHS CA1060AIINIGMS NIH HHS R01 GM022942NINDS NIH HHS NS24180NINDS NIH HHS NS32129NINDS NIH HHS R01 NS024180NINDS NIH HHS R01 NS032129PHS HHS 22942
6 · The paper itself

Abstract

purposeHuman remyelination promoting IgM mAbs target oligodendrocytes (OLs) and function in animal models of multiple sclerosis (MS). However, their mechanism of action is unknown. This study seeks to identify the cellular mechanism of action of a recombinant human IgM on OL survival.

methodsBinding of rHIgM22 to the surface of rat OLs was studied by co-localization with various markers. RHIgM22-mediated effects on apoptotic signaling in OLs, differentiation markers, and signaling molecules were detected by Western blotting and immunoprecipitation.

resultsRHIgM22 co-localized with integrin β3 but not other integrin β-chains in OLs. Downstream of integrin β3 we identified Src family kinase (SFK) Lyn as a key player of rHIgM22-mediated actions in OLs. Lyn immunoprecipitated in a complex together with integrin αvβ3 and PDGFαR. Lyn expression was 9-fold up-regulated and Lyn activation was 3-fold higher inrHIgM22-treated OL cultures compared with controls. RHIgM22 inhibited apoptotic signaling by greater than 10-fold reduction of caspase-3 and capsase-9 cleavage and reduced by 4-fold expression of differentiation markers MBP and MOG in OLs. SFK inhibitors PP2 and SU6656 inhibited Lyn activity and restored caspase-cleavage in OLs. A human IgM that did not promote remyelination and medium wereused as controls.

conclusionsrHIgM22 prevented apoptotic signaling andinhibited OL differentiation by Lyn implying thatIgM-mediated remyelination is due toprotection of OPC and OLs rather than promotion of OPC differentiation.

Indexed as

AnimalsAnimals, NewbornApoptosisBrainCaspase 3Cell DifferentiationDose-Response Relationship, DrugEnzyme InhibitorsFemaleGene Expression Regulation, EnzymologicHumansImmunoglobulin MImmunoprecipitationIndolesIntegrin beta3OligodendrogliaAG 1879Caspase 3Enzyme InhibitorsImmunoglobulin MIndolesIntegrin beta3lyn protein-tyrosine kinasePyrimidinesRecombinant Proteinssrc-Family KinasesSU 6656Sulfonamides

Identifiers

PMID20645409
PMCPMC2967300
OpenAlexW2038704767

What OpenQuestion holds

Textmetadata
LicenceTDM
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.