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

TitleSoluble NgR fusion protein modulates the proliferation of neural progenitor cells via the notch pathway
Authors
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
Citation
Neurochemical Research, 2011, v. 36 n. 12, p. 2363-2372 How to Cite?
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).
Persistent Identifierhttp://hdl.handle.net/10722/145028
ISSN
2014 Impact Factor: 2.593
2014 SCImago Journal Rankings: 0.900
PubMed Central ID
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorLi, Xen_HK
dc.contributor.authorSu, Hen_HK
dc.contributor.authorFu, QLen_HK
dc.contributor.authorGuo, Jen_HK
dc.contributor.authorLee, DHSen_HK
dc.contributor.authorSo, KFen_HK
dc.contributor.authorWu, Wen_HK
dc.date.accessioned2012-02-21T05:45:19Z-
dc.date.available2012-02-21T05:45:19Z-
dc.date.issued2011en_HK
dc.identifier.citationNeurochemical Research, 2011, v. 36 n. 12, p. 2363-2372en_HK
dc.identifier.issn0364-3190en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145028-
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).en_HK
dc.languageengen_US
dc.publisherSpringer New York LLC. The Journal's web site is located at http://springerlink.metapress.com/openurl.asp?genre=journal&issn=0364-3190en_HK
dc.relation.ispartofNeurochemical Researchen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong Licenseen_US
dc.rightsThe original publication is available at www.springerlink.comen_US
dc.rightsThe Author(s)-
dc.subjectMyelin-associated glycoproteinen_HK
dc.subjectNogo-66 receptoren_HK
dc.subjectNogoAen_HK
dc.subjectNotch1en_HK
dc.subjectRat neural progenitor cellsen_HK
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.titleSoluble NgR fusion protein modulates the proliferation of neural progenitor cells via the notch pathwayen_HK
dc.typeArticleen_HK
dc.identifier.emailSo, KF:hrmaskf@hkucc.hku.hken_HK
dc.identifier.emailWu, W:wtwu@hkucc.hku.hken_HK
dc.identifier.authoritySo, KF=rp00329en_HK
dc.identifier.authorityWu, W=rp00419en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1007/s11064-011-0562-7en_HK
dc.identifier.pmid21822922-
dc.identifier.pmcidPMC3207133-
dc.identifier.scopuseid_2-s2.0-80755130385en_HK
dc.identifier.hkuros197909-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80755130385&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume36en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2363en_HK
dc.identifier.epage2372en_HK
dc.identifier.eissn1573-6903en_US
dc.identifier.isiWOS:000296516500021-
dc.publisher.placeUnited Statesen_HK
dc.description.otherSpringer Open Choice, 21 Feb 2012en_US
dc.identifier.scopusauthoridLi, X=36065691100en_HK
dc.identifier.scopusauthoridSu, H=16317750200en_HK
dc.identifier.scopusauthoridFu, QL=23388762000en_HK
dc.identifier.scopusauthoridGuo, J=54414144900en_HK
dc.identifier.scopusauthoridLee, DHS=54414374400en_HK
dc.identifier.scopusauthoridSo, KF=34668391300en_HK
dc.identifier.scopusauthoridWu, W=7407081122en_HK
dc.identifier.citeulike9686888-

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