Article: Soluble NgR fusion protein modulates the proliferation of neural progenitor cells via the notch pathway

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TitleSoluble NgR fusion protein modulates the proliferation of neural progenitor cells via the notch pathway
AuthorsLi, X1 2
Su, H1
Fu, QL2
Guo, J1
Lee, DHS4
So, KF1 3
Wu, W1 3
KeywordsMyelin-associated glycoprotein
Nogo-66 receptor
NogoA
Notch1
Rat neural progenitor cells
Issue Date2011
PublisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0364-3190
CitationNeurochemical Research, 2011, v. 36 n. 12, p. 2363-2372 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s11064-011-0562-7
AbstractNogoA, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein are CNS myelin molecules that bind to the neuronal Nogo-66 receptor (NgR) and inhibit axon growth. The NgR antagonist, soluble NgR1-Fc protein (sNgR-Fc), facilitates axon regeneration by neutralizing the inhibitory effects of myelin proteins in experimental models of CNS injury. Here we aim to investigate the effect of sNgR-Fc on the proliferation of neural progenitor cells (NPCs). The hippocampus cells of embryonic rats were isolated and cultured in vitro. The expression of nestin, βIII-Tubulin, GFAP and Nogo-A on these cells was observed using immunocytochemistry. In order to investigate the effect on proliferation of NPCs, sNgR-Fc, MAG-Fc chimera and Notch1 blocker were added respectively. The total cell number for the proliferated NPCs was counted. BrdU was applied and the rate of proliferating cells was examined. The level of Notch1 was analyzed using Western blotting. We identified that NogoA is expressed in NPCs. sNgR-Fc significantly enhanced the proliferation of NPCs in vitro as indicated by BrdU labeling and total cell count. This proliferation effect was abolished by the administration of MAG suggesting specificity. In addition, we demonstrate that sNgR-Fc is a potent activator for Notch1 and Notch1 antagonist reversed the effect of sNgR-Fc on NPC proliferation. Our results suggest that sNgR-Fc may modulate Nogo activity to induce NPC proliferation via the Notch pathway. © 2011 The Author(s).
ISSN0364-3190
2011 Impact Factor: 2.24
2011 SCImago Journal Rankings: 0.168
DOIhttp://dx.doi.org/10.1007/s11064-011-0562-7
ISI Accession Number IDWOS:000296516500021
Funding AgencyGrant Number
Jessie Ho Professorship in Neuroscience
University of Hong Kong
National Basic Research Program of China (973Program)2011CB707501
Fundamental Research Funds for the Central Universities21609101
09ykpy25
09ykpy31
NSFC30801272
81071030
Science and Technology Foundation of Guangdong Province, China2010B031600089
Funding Information:

This study was supported by funding from the Jessie Ho Professorship in Neuroscience, grants from the University of Hong Kong, National Basic Research Program of China (973Program, 2011CB707501), the Fundamental Research Funds for the Central Universities (21609101), NSFC (30801272, 81071030), Science and Technology Foundation of Guangdong Province, China (2010B031600089), and the Fundamental Research Funds for the Central Universities (09ykpy25, 09ykpy31). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Biogen Idec, Inc. provided the sNgR-Fc in the study.

PubMed Central IDPMC3207133
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLi, X
dc.contributor.authorSu, H
dc.contributor.authorFu, QL
dc.contributor.authorGuo, J
dc.contributor.authorLee, DHS
dc.contributor.authorSo, KF
dc.contributor.authorWu, W
dc.date.accessioned2012-02-21T05:45:19Z
dc.date.available2012-02-21T05:45:19Z
dc.date.issued2011
dc.description.abstractNogoA, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein are CNS myelin molecules that bind to the neuronal Nogo-66 receptor (NgR) and inhibit axon growth. The NgR antagonist, soluble NgR1-Fc protein (sNgR-Fc), facilitates axon regeneration by neutralizing the inhibitory effects of myelin proteins in experimental models of CNS injury. Here we aim to investigate the effect of sNgR-Fc on the proliferation of neural progenitor cells (NPCs). The hippocampus cells of embryonic rats were isolated and cultured in vitro. The expression of nestin, βIII-Tubulin, GFAP and Nogo-A on these cells was observed using immunocytochemistry. In order to investigate the effect on proliferation of NPCs, sNgR-Fc, MAG-Fc chimera and Notch1 blocker were added respectively. The total cell number for the proliferated NPCs was counted. BrdU was applied and the rate of proliferating cells was examined. The level of Notch1 was analyzed using Western blotting. We identified that NogoA is expressed in NPCs. sNgR-Fc significantly enhanced the proliferation of NPCs in vitro as indicated by BrdU labeling and total cell count. This proliferation effect was abolished by the administration of MAG suggesting specificity. In addition, we demonstrate that sNgR-Fc is a potent activator for Notch1 and Notch1 antagonist reversed the effect of sNgR-Fc on NPC proliferation. Our results suggest that sNgR-Fc may modulate Nogo activity to induce NPC proliferation via the Notch pathway. © 2011 The Author(s).
dc.description.naturepublished_or_final_version
dc.description.otherSpringer Open Choice, 21 Feb 2012
dc.identifier.citationNeurochemical Research, 2011, v. 36 n. 12, p. 2363-2372 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s11064-011-0562-7
dc.identifier.citeulike9686888
dc.identifier.doihttp://dx.doi.org/10.1007/s11064-011-0562-7
dc.identifier.eissn1573-6903
dc.identifier.epage2372
dc.identifier.hkuros197909
dc.identifier.isiWOS:000296516500021
Funding AgencyGrant Number
Jessie Ho Professorship in Neuroscience
University of Hong Kong
National Basic Research Program of China (973Program)2011CB707501
Fundamental Research Funds for the Central Universities21609101
09ykpy25
09ykpy31
NSFC30801272
81071030
Science and Technology Foundation of Guangdong Province, China2010B031600089
Funding Information:

This study was supported by funding from the Jessie Ho Professorship in Neuroscience, grants from the University of Hong Kong, National Basic Research Program of China (973Program, 2011CB707501), the Fundamental Research Funds for the Central Universities (21609101), NSFC (30801272, 81071030), Science and Technology Foundation of Guangdong Province, China (2010B031600089), and the Fundamental Research Funds for the Central Universities (09ykpy25, 09ykpy31). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Biogen Idec, Inc. provided the sNgR-Fc in the study.

dc.identifier.issn0364-3190
2011 Impact Factor: 2.24
2011 SCImago Journal Rankings: 0.168
dc.identifier.issue12
dc.identifier.pmcidPMC3207133
dc.identifier.pmid21822922
dc.identifier.scopuseid_2-s2.0-80755130385
dc.identifier.spage2363
dc.identifier.urihttp://hdl.handle.net/10722/145028
dc.identifier.volume36
dc.languageeng
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0364-3190
dc.publisher.placeUnited States
dc.relation.ispartofNeurochemical Research
dc.relation.referencesReferences in Scopus
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.rightsThe original publication is available at www.springerlink.com
dc.rightsThe Author(s)
dc.subject.meshHippocampus - cytology
dc.subject.meshMyelin Proteins - biosynthesis - metabolism
dc.subject.meshMyelin-Associated Glycoprotein - pharmacology
dc.subject.meshReceptor, Notch1 - physiology
dc.subject.meshRecombinant Fusion Proteins - pharmacology
dc.subjectMyelin-associated glycoprotein
dc.subjectNogo-66 receptor
dc.subjectNogoA
dc.subjectNotch1
dc.subjectRat neural progenitor cells
dc.titleSoluble NgR fusion protein modulates the proliferation of neural progenitor cells via the notch pathway
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Sun Yat-Sen University
  3. Jinan University
  4. null